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<p><span>The Bioruptor® Pico is the latest innovation in shearing and represents a new breakthrough as an all-in-one shearing system capable of shearing samples from 150 bp to 1 kb. </span>Since 2004, Diagenode has accumulated <strong>shearing expertise</strong> to design the Bioruptor® Pico and guarantee the best experience with the <strong>sample preparation</strong> for <strong>number of applications -- in various fields of studies</strong> including environmental research, toxicology, genomics and epigenomics, cancer research, stem cells and development, neuroscience, clinical applications, agriculture, and many more.</p>
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<p>The Bioruptor Pico shearing accessories and consumables have been developed to allow <strong>flexibility in sample volumes</strong> (20 µl - 2 ml) and a <strong>fast parallel processing of samples</strong> (up to 16 samples simultaneously). <span>The built-in cooling system (Bioruptor® Cooler) ensures high precision <strong>temperature control</strong>. The <strong>user-friendly interface</strong> has been designed for any researcher, providing an easy and advanced modes that give both beginners and experienced users the right level of control. </span></p>
<p>In addition, Diagenode provides fully-validated tubes that remain <strong>budget-friendly with low operating cost</strong> (< 1€/$/DNA sample) and shearing kits for best sample quality. <span></span></p>
<p><strong>Application versatility</strong>:</p>
<ul>
<li>DNA shearing for Next-Generation-Sequencing</li>
<li>Chromatin shearing</li>
<li>RNA shearing</li>
<li>Protein extraction from tissues and cells (also for mass spectrometry)</li>
<li>FFPE DNA extraction</li>
<li>Protein aggregation studies</li>
<li>CUT&RUN - shearing of input DNA for NGS</li>
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<div style="background-color: #f1f3f4; margin: 10px; padding: 50px;">
<p><strong>Bioruptor Pico: Recommended for CUT&RUN sequencing for input DNA</strong><br /><br /> By combining antibody-targeted controlled cleavage by MNase and NGS, <strong>CUT&RUN sequencing</strong> can be used to identify protein-DNA binding sites genome-wide. CUT&RUN works by using the DNA cleaving activity of a Protein A-fused MNase to isolate DNA that is bound by a protein of interest. This targeted digestion is controlled by the addition of calcium, which MNase requires for its nuclease activity. After MNase digestion, short DNA fragments are released and can then be purified for subsequent library preparation and high-throughput sequencing. While CUT&RUN does not require mechanical shearing chromatin given the enzymatic approach, sonication is highly recommended for the fragmentation of the input DNA (used to compare the enriched sample) in order to be compatible with downstream NGS. The Bioruptor Pico is the ideal instrument of choice for generating optimal DNA fragments with a tight distribution, assuring excellent library prep and excellent sequencing results for your CUT&RUN assay.<br /><br /> <strong>Explore the Bioruptor Pico now.</strong></p>
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<div class="extra-spaced"><img alt="Bioruptor Sonication for DNA shearing for Next-Generation-Sequencing" src="https://www.diagenode.com/img/product/shearing_technologies/guarantie.png" /></div>
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'info2' => '<h3>Shearing Accessories</h3>
<table style="width: 641px;">
<thead>
<tr style="background-color: #dddddd; height: 37px;">
<td style="width: 300px; height: 37px;"><strong>Name</strong></td>
<td style="width: 171px; text-align: center; height: 37px;">Catalog number</td>
<td style="width: 160px; text-align: center; height: 37px;">Throughput</td>
</tr>
</thead>
<tbody>
<tr style="height: 38px;">
<td style="width: 300px; height: 38px;"><a href="https://www.diagenode.com/en/p/0-2-ml-tube-holder-dock-for-bioruptor-pico">Tube holder for 0.2 ml tubes</a></td>
<td style="width: 171px; text-align: center; height: 38px;"><span style="font-weight: 400;">B01201144</span></td>
<td style="width: 160px; text-align: center; height: 38px;"><span style="font-weight: 400;">16 samples</span></td>
</tr>
<tr style="height: 38px;">
<td style="width: 300px; height: 38px;"><a href="https://www.diagenode.com/en/p/0-65-ml-tube-holder-dock-for-bioruptor-pico">Tube holder for 0.65 ml tubes</a></td>
<td style="width: 171px; text-align: center; height: 38px;"><span style="font-weight: 400;">B01201143</span></td>
<td style="width: 160px; text-align: center; height: 38px;"><span style="font-weight: 400;">12 samples<br /></span></td>
</tr>
<tr style="height: 38px;">
<td style="width: 300px; height: 38px;"><a href="https://www.diagenode.com/en/p/1-5-ml-tube-holder-dock-for-bioruptor-pico">Tube holder for 1.5 ml tubes</a></td>
<td style="width: 171px; text-align: center; height: 38px;"><span style="font-weight: 400;">B01201140</span></td>
<td style="width: 160px; text-align: center; height: 38px;"><span style="font-weight: 400;">6 samples<br /></span></td>
</tr>
<tr style="height: 37px;">
<td style="width: 300px; height: 37px;"><a href="https://www.diagenode.com/en/p/15-ml-sonication-accessories-for-bioruptor-standard-plus-pico-1-pack">15 ml sonication accessories</a></td>
<td style="width: 171px; text-align: center; height: 37px;"><span style="font-weight: 400;">B01200016</span></td>
<td style="width: 160px; text-align: center; height: 37px;"><span style="font-weight: 400;">6 samples<br /></span></td>
</tr>
</tbody>
</table>
<h3>Shearing Consumables</h3>
<table style="width: 646px;">
<thead>
<tr style="background-color: #dddddd; height: 37px;">
<td style="width: 286px; height: 37px;"><strong>Name</strong></td>
<td style="width: 76px; height: 37px; text-align: center;">Catalog Number</td>
</tr>
</thead>
<tbody>
<tr style="height: 37px;">
<td style="width: 286px; height: 37px;"><a href="https://www.diagenode.com/en/p/02ml-microtubes-for-bioruptor-pico">0.2 ml Pico Microtubes</a></td>
<td style="width: 76px; height: 37px; text-align: center;"><span style="font-weight: 400;">C30010020</span></td>
</tr>
<tr style="height: 37px;">
<td style="width: 286px; height: 37px;"><a href="https://www.diagenode.com/en/p/0-65-ml-bioruptor-microtubes-500-tubes">0.65 ml Pico Microtubes</a></td>
<td style="width: 76px; height: 37px; text-align: center;"><span style="font-weight: 400;">C30010011</span></td>
</tr>
<tr style="height: 37px;">
<td style="width: 286px; height: 37px;"><a href="https://www.diagenode.com/en/p/1-5-ml-bioruptor-microtubes-with-caps-300-tubes">1.5 ml Pico Microtubes</a></td>
<td style="width: 76px; height: 37px; text-align: center;"><span style="font-weight: 400;">C30010016</span></td>
</tr>
<tr style="height: 37px;">
<td style="width: 286px; height: 37px;"><a href="https://www.diagenode.com/en/p/15-ml-bioruptor-tubes-50-pc">15 ml Pico Tubes</a></td>
<td style="width: 76px; height: 37px; text-align: center;"><span style="font-weight: 400;">C30010017</span></td>
</tr>
<tr style="height: 37px;">
<td style="width: 286px; height: 37px;"><a href="https://www.diagenode.com/en/p/15-ml-bioruptor-tubes-sonication-beads-50-rxns">15 ml Pico Tubes & sonication beads</a></td>
<td style="width: 76px; height: 37px; text-align: center;"><span style="font-weight: 400;">C01020031</span></td>
</tr>
</tbody>
</table>
<p><a href="https://www.diagenode.com/files/products/shearing_technology/bioruptor_accessories/TDS-BioruptorTubes.pdf">Find datasheet for Diagenode tubes here</a></p>
<p><a href="../documents/bioruptor-organigram-tubes">Which tubes for which Bioruptor®?</a></p>',
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'info3' => '<p>Diagenode has optimized a range of solutions for <strong>successful chromatin preparation</strong>. Chromatin EasyShear Kits together with the Pico ultrasonicator combine the benefits of efficient cell lysis and chromatin shearing, while keeping epitopes accessible to the antibody, critical for efficient chromatin immunoprecipitation. Each Chromatin EasyShear Kit provides optimized reagents and a thoroughly validated protocol according to your specific experimental needs. SDS concentration is adapted to each workflow taking into account target-specific requirements.</p>
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<h2>Kit choice guide</h2>
<table style="border: 0;" valign="center">
<tbody>
<tr style="background: #fff;">
<th class="text-center"></th>
<th class="text-center" style="font-size: 17px;">SAMPLE TYPE</th>
<th class="text-center" style="font-size: 17px;">SAMPLE INPUT</th>
<th class="text-center" style="font-size: 17px;">KIT</th>
<th class="text-center" style="font-size: 17px;">SDS<br /> CONCENTRATION</th>
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<tr style="background: #fff;">
<td colspan="7"></td>
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<tr style="background: #fff;">
<td rowspan="5"><img src="https://www.diagenode.com/img/label-histones.png" /></td>
<td class="text-center" style="border-bottom: 1px solid #dedede;">
<div class="label alert" style="font-size: 17px;">CELLS</div>
</td>
<td class="text-center" style="font-size: 17px; border-bottom: 1px solid #dedede;">< 100,000</td>
<td class="text-center" style="font-size: 17px; border-bottom: 1px solid #dedede;"><a href="https://www.diagenode.com/en/p/chromatin-shearing-optimization-kit-high-sds-100-million-cells">Chromatin EasyShear Kit<br />High SDS</a></td>
<td class="text-center" style="font-size: 17px; border-bottom: 1px solid #dedede;">1%</td>
<td class="text-center" style="border-bottom: 1px solid #dedede;"><img src="https://www.diagenode.com/img/cross-unvalid-green.jpg" width="18" height="20" /></td>
</tr>
<tr style="background: #fff; border-bottom: 1px solid #dedede;">
<td class="text-center">
<div class="label alert" style="font-size: 17px;">CELLS</div>
</td>
<td class="text-center" style="font-size: 17px;">> 100,000</td>
<td class="text-center" style="font-size: 17px;"><a href="https://www.diagenode.com/en/p/chromatin-easyshear-kit-ultra-low-sds">Chromatin EasyShear Kit<br />Ultra Low SDS</a></td>
<td class="text-center" style="font-size: 17px;">< 0.1%</td>
<td class="text-center"><img src="https://www.diagenode.com/img/valid.png" width="20" height="16" /></td>
</tr>
<tr style="background: #fff; border-bottom: 1px solid #dedede;">
<td class="text-center">
<div class="label alert" style="font-size: 17px;">TISSUE</div>
</td>
<td class="text-center"></td>
<td class="text-center" style="font-size: 17px;"><a href="https://www.diagenode.com/en/p/chromatin-easyshear-kit-ultra-low-sds">Chromatin EasyShear Kit<br />Ultra Low SDS</a></td>
<td class="text-center" style="font-size: 17px;">< 0.1%</td>
<td class="text-center"><img src="https://www.diagenode.com/img/valid.png" width="20" height="16" /></td>
</tr>
<tr style="background: #fff; border-bottom: 1px solid #dedede;">
<td class="text-center">
<div class="label alert" style="font-size: 17px;">PLANT TISSUE</div>
</td>
<td class="text-center"></td>
<td class="text-center" style="font-size: 17px;"><a href="https://www.diagenode.com/en/p/chromatin-shearing-plant-chip-seq-kit">Chromatin EasyShear Kit<br />for Plant</a></td>
<td class="text-center" style="font-size: 17px;">0.5%</td>
<td class="text-center"><img src="https://www.diagenode.com/img/valid.png" width="20" height="16" /></td>
</tr>
<tr style="background: #fff;">
<td class="text-center">
<div class="label alert" style="font-size: 17px;">FFPE SAMPLES</div>
</td>
<td class="text-center"></td>
<td class="text-center" style="font-size: 17px;"><a href="https://www.diagenode.com/en/p/chromatin-easyshear-kit-low-sds">Chromatin EasyShear Kit<br />Low SDS</a></td>
<td class="text-center" style="font-size: 17px;">0.2%</td>
<td class="text-center"><img src="https://www.diagenode.com/img/valid.png" width="20" height="16" /></td>
</tr>
<tr style="background: #fff;">
<td colspan="7"></td>
</tr>
<tr style="background: #fff;">
<td rowspan="6"><img src="https://www.diagenode.com/img/label-tf.png" /></td>
<td colspan="6"></td>
</tr>
<tr style="background: #fff;">
<td colspan="6"></td>
</tr>
<tr style="background: #fff;">
<td class="text-center">
<div class="label alert" style="font-size: 17px;">CELLS</div>
</td>
<td class="text-center"></td>
<td rowspan="3" class="text-center" style="font-size: 17px;"><a href="https://www.diagenode.com/en/p/chromatin-easyshear-kit-low-sds">Chromatin EasyShear Kit<br />Low SDS</a></td>
<td rowspan="3" class="text-center" style="font-size: 17px;">0.2%</td>
<td rowspan="3" class="text-center"><img src="https://www.diagenode.com/img/valid.png" width="20" height="16" /></td>
</tr>
<tr style="background: #fff;">
<td class="text-center">
<div class="label alert" style="font-size: 17px;">TISSUE</div>
</td>
<td class="text-center"></td>
</tr>
<tr style="background: #fff;">
<td class="text-center">
<div class="label alert" style="font-size: 17px;">FFPE SAMPLES</div>
</td>
<td class="text-center"></td>
</tr>
<tr style="background: #fff;">
<td colspan="6"></td>
</tr>
</tbody>
</table>
<div class="extra-spaced">
<h3>Guide for optimal chromatin preparation using Chromatin EasyShear Kits <i class="fa fa-arrow-circle-right"></i> <a href="https://www.diagenode.com/pages/chromatin-prep-easyshear-kit-guide">Read more</a></h3>
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<div class="small-12 medium-12 large-12 columns">In recent years, advances in Next-Generation Sequencing (NGS) have revolutionized genomics and biology. This growth has fueled demands on upstream techniques for optimal sample preparation and genomic library construction. One of the most critical aspects of optimal library preparation is the quality of the DNA to be sequenced. The DNA must first be effectively and consistently sheared into the appropriate fragment size (depending on the sequencing platform) to enable sensitive and reliable NGS results. The <strong>Bioruptor</strong><sup>®</sup> <strong>Pico</strong> and the <strong>Megaruptor</strong><sup>®</sup> provide superior sample yields, fragment size, and consistency, which are essential for Next-Generation Sequencing workflows. Follow our guidelines and find the good parameters for your expected DNA size: <a href="https://pybrevet.typeform.com/to/o8cQfM">DNA shearing with the Bioruptor<sup>®</sup></a>.</div>
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<div class="small-7 medium-7 large-7 columns text-center"><img src="https://www.diagenode.com/img/applications/true-flexibility-with-br-ngs.jpg" /></div>
<div class="small-5 medium-5 large-5 columns"><small><strong>Programmable DNA size distribution and high reproducibility with Bioruptor<sup>®</sup> Pico using 0.65 (panel A) or 0.1 ml (panel B) microtubes</strong>. <b>Panel A:</b> 200 bp after 13 cycles (13 sec ON/OFF) using 100 µl volume. Average size: 204; CV%:1.89%). <b>Panel B:</b> 200 bp after 20 cycles (30 sec ON/OFF) using 10 µl volume. (Average size: 215 bp; CV%: 6.6%). <b>Panel A & B:</b> peak electropherogram view. <b>Panel C & D:</b> virtual gel view.</small></div>
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<p><br /><br /></p>
<div class="row">
<div class="small-10 medium-10 large-10 columns text-center end small-offset-1"><img src="https://www.diagenode.com/img/applications/megaruptor-short-frag.jpg" /></div>
<div class="small-12 medium-12 large-12 columns"><small><strong> Reproducible and narrow DNA size distribution with Megaruptor® using short fragment size Hydropores Validation using two different DNA sources and two different methods of analysis. A:</strong> Shearing of lambda phage genomic DNA (20 ng/μl; 150 μl/sample) sheared at different speed settings and analyzed on 1% agarose gel. <strong>B:</strong> Bioanalyzer profiles of human genomic DNA (20 ng/μl; 150 μl/sample) sheared at different software settings of 2 and 5 kb. Three independent experiments were run for each setting. (Agilent DNA 12000 kit was used for separation and fragment sizing).</small></div>
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<p><br /><br /></p>
<div class="row">
<div class="small-4 medium-4 large-4 columns text-center"><img src="https://www.diagenode.com/img/applications/megaruptor-long-frag.jpg" /></div>
<div class="small-8 medium-8 large-8 columns"><small><strong> Demonstrated shearing to fragment sizes between 15 kb and 75 kb with Megaruptor® using long fragment size Hydropores. </strong>Image shows DNA size distribution of human genomic DNA sheared with long fragment Hydropores. DNA was analyzed by pulsed field gel electrophoresis (PFGE) in 1% agarose gel and a mean size of smears was estimated using Image Lab 4.1 software.<br /> * indicates unsheared DNA </small></div>
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<div class="small-12 medium-12 large-12 columns">The most important steps for a successful ChIP include both cell fixation and lysis, and chromatin shearing. Researchers often overlook the critical nature of both of these steps. Eliminating inconsistencies in the shearing step, <strong>Diagenode's Bioruptor</strong><sup>®</sup> uses state-of-the-art ultrasound <strong>ACT</strong> (<strong>A</strong>daptive <strong>C</strong>avitation <strong>T</strong>echnology) to efficiently shear chromatin. ACT enables the highest chromatin quality for high IP efficiency and sensitivity for ChIP experiments with gentle yet highly effective shearing forces. Additionally, the Bioruptor<sup>®</sup> provides a precisely controlled temperature environment that preserves chromatin from heat degradation such that protein-DNA complexes are well-preserved for sensitive, unbiased, and accurate ChIP.<br /><br /> <strong>Diagenode's Bioruptor</strong><sup>®</sup> is the instrument of choice for chromatin shearing used for a number of downstream applications such as qPCR and ChIP-seq that require optimally sheared, unbiased chromatin.</div>
<div class="small-12 medium-12 large-12 columns text-center"><br /><img src="https://www.diagenode.com/img/applications/pico_dna_shearing_fig2.png" /></div>
<div class="small-10 medium-10 large-10 columns end small-offset-1"><small> <br /><strong>Panel A, 10 µl volume:</strong> Chromatin samples are sheared for 10, 20 and 30 cycles of 30 sec ON/30 sec OFF with the Bioruptor® Pico using 0.1 ml Bioruptor® Microtubes (Cat. No. B01200041). <strong>Panel B, 100 µl volume:</strong> Chromatin samples are sheared for 10 cycles of 30 sec ON/30 sec OFF with the Bioruptor® Pico using 0.65 ml Bioruptor® Microtubes (Cat. No. WA-005-0500). <strong>Panel C, 300 µl volume:</strong> Chromatin samples are sheared for 5, 10 and 15 cycles of 30 sec ON/30 sec OFF with the Bioruptor® Pico using using 1.5 ml Bioruptor microtubes (Cat. No. C30010016). Prior to de-crosslinking, samples are treated with RNase cocktail mixture at 37°C during 1 hour. The sheared chromatin is then de-crosslinked overnight and phenol/chloroform purified as described in the kit manual. 10 µl of DNA (equivalent of 500, 000 cells) are analyzed on a 2% agarose gel (MW corresponds to the 100 bp DNA molecular weight marker).</small></div>
<div class="small-12 medium-12 large-12 columns"><br /><br /></div>
<div class="small-12 medium-12 large-12 columns">
<p>It is important to establish optimal conditions to shear crosslinked chromatin to get the correct fragment sizes needed for ChIP. Usually this process requires both optimizing sonication conditions as well as optimizing SDS concentration, which is laborious. With the Chromatin Shearing Optimization Kits, optimization is fast and easy - we provide optimization reagents with varying concentrations of SDS. Moreover, our Chromatin Shearing Optimization Kits can be used for the optimization of chromatin preparation with our kits for ChIP.</p>
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<div class="small-12 medium-12 large-12 columns">
<div class="page" title="Page 7">
<table>
<tbody>
<tr valign="middle">
<td></td>
<td style="text-align: center;"><strong><a href="https://www.diagenode.com/p/chromatin-shearing-optimization-kit-low-sds-100-million-cells">Chromatin Shearing Kit Low SDS (for Histone)</a></strong></td>
<td style="text-align: center;"><strong><a href="https://www.diagenode.com/p/chromatin-shearing-optimization-kit-low-sds-for-tfs-25-rxns">Chromatin Shearing Kit Low SDS (for TF)</a></strong></td>
<td style="text-align: center;"><strong><a href="https://www.diagenode.com/p/chromatin-shearing-optimization-kit-high-sds-100-million-cells">Chromatin Shearing Kit High SDS</a></strong></td>
<td style="text-align: center;"><strong><a href="https://www.diagenode.com/p/chromatin-shearing-optimization-kit-medium-sds-100-million-cells">Chromatin Shearing Kit (for Plant)</a></strong></td>
</tr>
<tr valign="middle" style="background-color: #fff;">
<td>
<p><strong>SDS concentration</strong></p>
</td>
<td style="text-align: center;">
<p>< 0.1%</p>
</td>
<td style="text-align: center;">
<p>0.2%</p>
</td>
<td style="text-align: center;">
<p>1%</p>
</td>
<td style="text-align: center;">
<p>0.5%</p>
</td>
</tr>
<tr valign="middle" style="background-color: #fff;">
<td>
<p><strong>Nuclei isolation</strong></p>
</td>
<td style="text-align: center;">
<p>Yes</p>
</td>
<td style="text-align: center;">
<p>Yes</p>
</td>
<td style="text-align: center;">
<p>No</p>
</td>
<td style="text-align: center;">
<p>Yes</p>
</td>
</tr>
<tr valign="middle" style="background-color: #fff;">
<td>
<p><strong>Allows for shearing of... cells/tissue</strong></p>
</td>
<td style="text-align: center;">
<p>100 million cells</p>
</td>
<td style="text-align: center;">
<p>100 million cells</p>
</td>
<td style="text-align: center;">
<p>100 million cells</p>
</td>
<td style="text-align: center;">
<p>up to 25 g of tissue</p>
</td>
</tr>
<tr valign="middle" style="background-color: #fff;">
<td>
<p><strong>Corresponding to shearing buffers from</strong></p>
</td>
<td style="text-align: center;">
<p><a href="https://www.diagenode.com/en/p/ideal-chip-seq-kit-x24-24-rxns">iDeal ChIP-seq kit for Histones</a></p>
</td>
<td style="text-align: center;">
<p><a href="https://www.diagenode.com/en/p/ideal-chip-seq-kit-for-transcription-factors-x24-24-rxns">iDeal ChIP-seq Kit for Transcription Factors</a></p>
<p><a href="https://www.diagenode.com/en/p/ideal-chip-qpcr-kit">iDeal ChIP qPCR kit</a></p>
</td>
<td style="text-align: center;">
<p><a href="https://www.diagenode.com/en/p/true-microchip-kit-x16-16-rxns">True MicroChIP kit</a></p>
</td>
<td style="text-align: center;">
<p><a href="https://www.diagenode.com/en/p/universal-plant-chip-seq-kit-x24-24-rxns">Universal Plant ChIP-seq kit</a></p>
</td>
</tr>
</tbody>
</table>
<p><em><span style="font-weight: 400;">Table comes from our </span><a href="https://www.diagenode.com/protocols/bioruptor-pico-chromatin-preparation-guide"><span style="font-weight: 400;">Guide for successful chromatin preparation using the Bioruptor® Pico</span></a></em></p>
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<div class="large-12 columns">Diagenode's high yields FFPE DNA extraction using Bioruptor<sup><span>®</span></sup> is a superior method for extracting DNA for Next-Gen Sequencing. Our FFPE DNA Extraction kit contains optimized reagents that are added directly to the FFPE samples to remove paraffin with no toxic reagents, digest tissues, and purify DNA with high yields and low sample degradation. The DNA can then be analyzed by traditional methods or can be sheared with the Bioruptor<sup>®</sup> Pico ultrasonicator for downstream NGS library prep using the MicroPlex Library Preparation Kit.</div>
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<p><span>The 1.5 ml Bioruptor</span><span>® </span><span>Microtubes </span><strong>C30010016 </strong><span>for chromatin shearing strongly improve chromatin sonication efficiency. These tubes have been thoroughly validated for use on the Bioruptor</span><span>® </span><span>Pico (B01060001) and are strongly recommended for DNA and chromatin shearing applications using this instrument. </span></p>
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'name' => 'CREBBP/EP300 acetyltransferase inhibition disrupts FOXA1-bound enhancers to inhibit the proliferation of ER+ breast cancer cells.',
'authors' => 'Bommi-Reddy A. et al.',
'description' => '<p><span>Therapeutic targeting of the estrogen receptor (ER) is a clinically validated approach for estrogen receptor positive breast cancer (ER+ BC), but sustained response is limited by acquired resistance. Targeting the transcriptional coactivators required for estrogen receptor activity represents an alternative approach that is not subject to the same limitations as targeting estrogen receptor itself. In this report we demonstrate that the acetyltransferase activity of coactivator paralogs CREBBP/EP300 represents a promising therapeutic target in ER+ BC. Using the potent and selective inhibitor CPI-1612, we show that CREBBP/EP300 acetyltransferase inhibition potently suppresses in vitro and in vivo growth of breast cancer cell line models and acts in a manner orthogonal to directly targeting ER. CREBBP/EP300 acetyltransferase inhibition suppresses ER-dependent transcription by targeting lineage-specific enhancers defined by the pioneer transcription factor FOXA1. These results validate CREBBP/EP300 acetyltransferase activity as a viable target for clinical development in ER+ breast cancer.</span></p>',
'date' => '2022-03-30',
'pmid' => 'https://pubmed.ncbi.nlm.nih.gov/35353838/',
'doi' => '10.1371/journal.pone.0262378',
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'name' => 'Exploring the virulence gene interactome with CRISPR/dCas9 in the humanmalaria parasite.',
'authors' => 'Bryant, JM and Baumgarten, S and Dingli, F and Loew, D and Sinha, A andClaës, A and Preiser, PR and Dedon, PC and Scherf, A',
'description' => '<p>Mutually exclusive expression of the var multigene family is key to immune evasion and pathogenesis in Plasmodium falciparum, but few factors have been shown to play a direct role. We adapted a CRISPR-based proteomics approach to identify novel factors associated with var genes in their natural chromatin context. Catalytically inactive Cas9 ("dCas9") was targeted to var gene regulatory elements, immunoprecipitated, and analyzed with mass spectrometry. Known and novel factors were enriched including structural proteins, DNA helicases, and chromatin remodelers. Functional characterization of PfISWI, an evolutionarily divergent putative chromatin remodeler enriched at the var gene promoter, revealed a role in transcriptional activation. Proteomics of PfISWI identified several proteins enriched at the var gene promoter such as acetyl-CoA synthetase, a putative MORC protein, and an ApiAP2 transcription factor. These findings validate the CRISPR/dCas9 proteomics method and define a new var gene-associated chromatin complex. This study establishes a tool for targeted chromatin purification of unaltered genomic loci and identifies novel chromatin-associated factors potentially involved in transcriptional control and/or chromatin organization of virulence genes in the human malaria parasite.</p>',
'date' => '2020-08-02',
'pmid' => 'http://www.pubmed.gov/32816370',
'doi' => 'https://dx.doi.org/10.15252%2Fmsb.20209569',
'modified' => '2020-12-18 13:26:33',
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'name' => 'Proteomics Links Ubiquitin Chain Topology Change to Transcription Factor Activation.',
'authors' => 'Li Y, Dammer EB, Gao Y, Lan Q, Villamil MA, Duong DM, Zhang C, Ping L, Lauinger L, Flick K, Xu Z, Wei W, Xing X, Chang L, Jin J, Hong X, Zhu Y, Wu J, Deng Z, He F, Kaiser P, Xu P',
'description' => '<p>A surprising complexity of ubiquitin signaling has emerged with identification of different ubiquitin chain topologies. However, mechanisms of how the diverse ubiquitin codes control biological processes remain poorly understood. Here, we use quantitative whole-proteome mass spectrometry to identify yeast proteins that are regulated by lysine 11 (K11)-linked ubiquitin chains. The entire Met4 pathway, which links cell proliferation with sulfur amino acid metabolism, was significantly affected by K11 chains and selected for mechanistic studies. Previously, we demonstrated that a K48-linked ubiquitin chain represses the transcription factor Met4. Here, we show that efficient Met4 activation requires a K11-linked topology. Mechanistically, our results propose that the K48 chain binds to a topology-selective tandem ubiquitin binding region in Met4 and competes with binding of the basal transcription machinery to the same region. The change to K11-enriched chain architecture releases this competition and permits binding of the basal transcription complex to activate transcription.</p>',
'date' => '2019-08-06',
'pmid' => 'http://www.pubmed.gov/31444107',
'doi' => '10.1016/j.molcel.2019.07.001',
'modified' => '2019-10-03 09:21:23',
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'name' => 'The role of TCF3 as potential master regulator in blastemal Wilms tumors.',
'authors' => 'Kehl T, Schneider L, Kattler K, Stöckel D, Wegert J, Gerstner N, Ludwig N, Distler U, Tenzer S, Gessler M, Walter J, Keller A, Graf N, Meese E, Lenhof HP',
'description' => '<p>Wilms tumors are the most common type of pediatric kidney tumors. While the overall prognosis for patients is favorable, especially tumors that exhibit a blastemal subtype after preoperative chemotherapy have a poor prognosis. For an improved risk assessment and therapy stratification, it is essential to identify the driving factors that are distinctive for this aggressive subtype. In our study, we compared gene expression profiles of 33 tumor biopsies (17 blastemal and 16 other tumors) after neoadjuvant chemotherapy. The analysis of this dataset using the Regulator Gene Association Enrichment algorithm successfully identified several biomarkers and associated molecular mechanisms that distinguish between blastemal and nonblastemal Wilms tumors. Specifically, regulators involved in embryonic development and epigenetic processes like chromatin remodeling and histone modification play an essential role in blastemal tumors. In this context, we especially identified TCF3 as the central regulatory element. Furthermore, the comparison of ChIP-Seq data of Wilms tumor cell cultures from a blastemal mouse xenograft and a stromal tumor provided further evidence that the chromatin states of blastemal cells share characteristics with embryonic stem cells that are not present in the stromal tumor cell line. These stem-cell like characteristics could potentially add to the increased malignancy and chemoresistance of the blastemal subtype. Along with TCF3, we detected several additional biomarkers that are distinctive for blastemal Wilms tumors after neoadjuvant chemotherapy and that may provide leads for new therapeutic regimens.</p>',
'date' => '2019-03-15',
'pmid' => 'http://www.pubmed.gov/30155889',
'doi' => '10.1002/ijc.31834',
'modified' => '2019-03-21 17:10:17',
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'id' => '3727',
'name' => 'Transcriptome-wide dynamics of extensive m6A mRNA methylation during Plasmodium falciparum blood-stage development',
'authors' => 'Sebastian Baumgarten, Jessica M. Bryant, Ameya Sinha, Thibaud Reyser, Peter R. Preiser, Peter C. Dedon, Artur Scherf',
'description' => '<p>Malaria pathogenesis results from the asexual replication of Plasmodium falciparum within human red blood cells, which relies on a precisely timed cascade of gene expression over a 48-hour life cycle. Although substantial post-transcriptional regulation of this hardwired program has been observed, it remains unclear how these processes are mediated on a transcriptome-wide level. To this end, we identified mRNA modifications in the P. falciparum transcriptome and performed a comprehensive characterization of N6-methyladenosine (m6A) over the course of blood stage development. Using mass spectrometry and m6A RNA sequencing, we demonstrate that m6A is highly developmentally regulated, exceeding m6A levels known in any other eukaryote. We identify an evolutionarily conserved m6A writer complex and show that knockdown of the putative m6A methyltransferase by CRISPR interference leads to increased levels of transcripts that normally contain m6A. In accordance, we find an inverse correlation between m6A status and mRNA stability or translational efficiency. Our data reveal the crucial role of extensive m6A mRNA methylation in dynamically fine-tuning the transcriptional program of a unicellular eukaryote as well as a new ‘epitranscriptomic’ layer of gene regulation in malaria parasites.</p>',
'date' => '2019-03-09',
'pmid' => 'https://www.nature.com/articles/s41564-019-0521-7',
'doi' => '10.1101/572891.',
'modified' => '2022-05-18 19:27:33',
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'name' => 'Dot1 promotes H2B ubiquitination by a methyltransferase-independent mechanism.',
'authors' => 'van Welsem T, Korthout T, Ekkebus R, Morais D, Molenaar TM, van Harten K, Poramba-Liyanage DW, Sun SM, Lenstra TL, Srivas R, Ideker T, Holstege FCP, van Attikum H, El Oualid F, Ovaa H, Stulemeijer IJE, Vlaming H, van Leeuwen F',
'description' => '<p>The histone methyltransferase Dot1 is conserved from yeast to human and methylates lysine 79 of histone H3 (H3K79) on the core of the nucleosome. H3K79 methylation by Dot1 affects gene expression and the response to DNA damage, and is enhanced by monoubiquitination of the C-terminus of histone H2B (H2Bub1). To gain more insight into the functions of Dot1, we generated genetic interaction maps of increased-dosage alleles of DOT1. We identified a functional relationship between increased Dot1 dosage and loss of the DUB module of the SAGA co-activator complex, which deubiquitinates H2Bub1 and thereby negatively regulates H3K79 methylation. Increased Dot1 dosage was found to promote H2Bub1 in a dose-dependent manner and this was exacerbated by the loss of SAGA-DUB activity, which also caused a negative genetic interaction. The stimulatory effect on H2B ubiquitination was mediated by the N-terminus of Dot1, independent of methyltransferase activity. Our findings show that Dot1 and H2Bub1 are subject to bi-directional crosstalk and that Dot1 possesses chromatin regulatory functions that are independent of its methyltransferase activity.</p>',
'date' => '2018-09-08',
'pmid' => 'http://www.pubmed.gov/30203048',
'doi' => '10.1093/nar/gky801',
'modified' => '2018-11-09 12:13:19',
'created' => '2018-11-08 12:59:45',
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'name' => 'BET protein inhibition sensitizes glioblastoma cells to temozolomidetreatment by attenuating MGMT expression',
'authors' => 'Tancredi A. et al.',
'description' => '<p>Bromodomain and extra-terminal tail (BET) proteins have been identified as potential epigenetic targets in cancer, including glioblastoma. These epigenetic modifiers link the histone code to gene transcription that can be disrupted with small molecule BET inhibitors (BETi). With the aim of developing rational combination treatments for glioblastoma, we analyzed BETi-induced differential gene expression in glioblastoma derived-spheres, and identified 6 distinct response patterns. To uncover emerging actionable vulnerabilities that can be targeted with a second drug, we extracted the 169 significantly disturbed DNA Damage Response genes and inspected their response pattern. The most prominent candidate with consistent downregulation, was the O-6-methylguanine-DNA methyltransferase (MGMT) gene, a known resistance factor for alkylating agent therapy in glioblastoma. BETi not only reduced MGMT expression in GBM cells, but also inhibited its induction, typically observed upon temozolomide treatment. To determine the potential clinical relevance, we evaluated the specificity of the effect on MGMT expression and MGMT mediated treatment resistance to temozolomide. BETi-mediated attenuation of MGMT expression was associated with reduction of BRD4- and Pol II-binding at the MGMT promoter. On the functional level, we demonstrated that ectopic expression of MGMT under an unrelated promoter was not affected by BETi, while under the same conditions, pharmacologic inhibition of MGMT restored the sensitivity to temozolomide, reflected in an increased level of g-H2AX, a proxy for DNA double-strand breaks. Importantly, expression of MSH6 and MSH2, which are required for sensitivity to unrepaired O6-methylGuanin-lesions, was only briefly affected by BETi. Taken together, the addition of BET-inhibitors to the current standard of care, comprising temozolomide treatment, may sensitize the 50\% of patients whose glioblastoma exert an unmethylated MGMT promoter.</p>',
'date' => '0000-00-00',
'pmid' => 'https://www.researchsquare.com/article/rs-1832996/v1',
'doi' => '10.21203/rs.3.rs-1832996/v1',
'modified' => '2022-11-24 10:06:26',
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<div class="small-12 columns" >
<h6 style="height:60px">Picoruptor 2 sonication device </h6>
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<p><strong><input name="data[Cart][quantity]" placeholder="1" value="1" min="1" style="width:60px;display:inline" type="number" id="CartQuantity" required="required"/></strong>Tube holder for 1.5 ml tubes - Bioruptor<sup>®</sup> Pico個カートに追加。</p>
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<h6 style="height:60px">Tube holder for 1.5 ml tubes - Picoruptor</h6>
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<p><span>The Bioruptor® Pico is the latest innovation in shearing and represents a new breakthrough as an all-in-one shearing system capable of shearing samples from 150 bp to 1 kb. </span>Since 2004, Diagenode has accumulated <strong>shearing expertise</strong> to design the Bioruptor® Pico and guarantee the best experience with the <strong>sample preparation</strong> for <strong>number of applications -- in various fields of studies</strong> including environmental research, toxicology, genomics and epigenomics, cancer research, stem cells and development, neuroscience, clinical applications, agriculture, and many more.</p>
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<p>The Bioruptor Pico shearing accessories and consumables have been developed to allow <strong>flexibility in sample volumes</strong> (20 µl - 2 ml) and a <strong>fast parallel processing of samples</strong> (up to 16 samples simultaneously). <span>The built-in cooling system (Bioruptor® Cooler) ensures high precision <strong>temperature control</strong>. The <strong>user-friendly interface</strong> has been designed for any researcher, providing an easy and advanced modes that give both beginners and experienced users the right level of control. </span></p>
<p>In addition, Diagenode provides fully-validated tubes that remain <strong>budget-friendly with low operating cost</strong> (< 1€/$/DNA sample) and shearing kits for best sample quality. <span></span></p>
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<p><strong>Bioruptor Pico: Recommended for CUT&RUN sequencing for input DNA</strong><br /><br /> By combining antibody-targeted controlled cleavage by MNase and NGS, <strong>CUT&RUN sequencing</strong> can be used to identify protein-DNA binding sites genome-wide. CUT&RUN works by using the DNA cleaving activity of a Protein A-fused MNase to isolate DNA that is bound by a protein of interest. This targeted digestion is controlled by the addition of calcium, which MNase requires for its nuclease activity. After MNase digestion, short DNA fragments are released and can then be purified for subsequent library preparation and high-throughput sequencing. While CUT&RUN does not require mechanical shearing chromatin given the enzymatic approach, sonication is highly recommended for the fragmentation of the input DNA (used to compare the enriched sample) in order to be compatible with downstream NGS. The Bioruptor Pico is the ideal instrument of choice for generating optimal DNA fragments with a tight distribution, assuring excellent library prep and excellent sequencing results for your CUT&RUN assay.<br /><br /> <strong>Explore the Bioruptor Pico now.</strong></p>
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<td style="width: 171px; text-align: center; height: 38px;"><span style="font-weight: 400;">B01201144</span></td>
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<td style="width: 171px; text-align: center; height: 38px;"><span style="font-weight: 400;">B01201143</span></td>
<td style="width: 160px; text-align: center; height: 38px;"><span style="font-weight: 400;">12 samples<br /></span></td>
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<tr style="height: 38px;">
<td style="width: 300px; height: 38px;"><a href="https://www.diagenode.com/en/p/1-5-ml-tube-holder-dock-for-bioruptor-pico">Tube holder for 1.5 ml tubes</a></td>
<td style="width: 171px; text-align: center; height: 38px;"><span style="font-weight: 400;">B01201140</span></td>
<td style="width: 160px; text-align: center; height: 38px;"><span style="font-weight: 400;">6 samples<br /></span></td>
</tr>
<tr style="height: 37px;">
<td style="width: 300px; height: 37px;"><a href="https://www.diagenode.com/en/p/15-ml-sonication-accessories-for-bioruptor-standard-plus-pico-1-pack">15 ml sonication accessories</a></td>
<td style="width: 171px; text-align: center; height: 37px;"><span style="font-weight: 400;">B01200016</span></td>
<td style="width: 160px; text-align: center; height: 37px;"><span style="font-weight: 400;">6 samples<br /></span></td>
</tr>
</tbody>
</table>
<h3>Shearing Consumables</h3>
<table style="width: 646px;">
<thead>
<tr style="background-color: #dddddd; height: 37px;">
<td style="width: 286px; height: 37px;"><strong>Name</strong></td>
<td style="width: 76px; height: 37px; text-align: center;">Catalog Number</td>
</tr>
</thead>
<tbody>
<tr style="height: 37px;">
<td style="width: 286px; height: 37px;"><a href="https://www.diagenode.com/en/p/02ml-microtubes-for-bioruptor-pico">0.2 ml Pico Microtubes</a></td>
<td style="width: 76px; height: 37px; text-align: center;"><span style="font-weight: 400;">C30010020</span></td>
</tr>
<tr style="height: 37px;">
<td style="width: 286px; height: 37px;"><a href="https://www.diagenode.com/en/p/0-65-ml-bioruptor-microtubes-500-tubes">0.65 ml Pico Microtubes</a></td>
<td style="width: 76px; height: 37px; text-align: center;"><span style="font-weight: 400;">C30010011</span></td>
</tr>
<tr style="height: 37px;">
<td style="width: 286px; height: 37px;"><a href="https://www.diagenode.com/en/p/1-5-ml-bioruptor-microtubes-with-caps-300-tubes">1.5 ml Pico Microtubes</a></td>
<td style="width: 76px; height: 37px; text-align: center;"><span style="font-weight: 400;">C30010016</span></td>
</tr>
<tr style="height: 37px;">
<td style="width: 286px; height: 37px;"><a href="https://www.diagenode.com/en/p/15-ml-bioruptor-tubes-50-pc">15 ml Pico Tubes</a></td>
<td style="width: 76px; height: 37px; text-align: center;"><span style="font-weight: 400;">C30010017</span></td>
</tr>
<tr style="height: 37px;">
<td style="width: 286px; height: 37px;"><a href="https://www.diagenode.com/en/p/15-ml-bioruptor-tubes-sonication-beads-50-rxns">15 ml Pico Tubes & sonication beads</a></td>
<td style="width: 76px; height: 37px; text-align: center;"><span style="font-weight: 400;">C01020031</span></td>
</tr>
</tbody>
</table>
<p><a href="https://www.diagenode.com/files/products/shearing_technology/bioruptor_accessories/TDS-BioruptorTubes.pdf">Find datasheet for Diagenode tubes here</a></p>
<p><a href="../documents/bioruptor-organigram-tubes">Which tubes for which Bioruptor®?</a></p>',
'label3' => 'Available shearing Kits',
'info3' => '<p>Diagenode has optimized a range of solutions for <strong>successful chromatin preparation</strong>. Chromatin EasyShear Kits together with the Pico ultrasonicator combine the benefits of efficient cell lysis and chromatin shearing, while keeping epitopes accessible to the antibody, critical for efficient chromatin immunoprecipitation. Each Chromatin EasyShear Kit provides optimized reagents and a thoroughly validated protocol according to your specific experimental needs. SDS concentration is adapted to each workflow taking into account target-specific requirements.</p>
<p>For best results, choose your desired ChIP kit followed by the corresponding Chromatin EasyShear Kit (to optimize chromatin shearing ). The Chromatin EasyShear Kits can be used independently of Diagenode’s ChIP kits for chromatin preparation prior to any chromatin immunoprecipitation protocol. Choose an appropriate kit for your specific experimental needs.</p>
<h2>Kit choice guide</h2>
<table style="border: 0;" valign="center">
<tbody>
<tr style="background: #fff;">
<th class="text-center"></th>
<th class="text-center" style="font-size: 17px;">SAMPLE TYPE</th>
<th class="text-center" style="font-size: 17px;">SAMPLE INPUT</th>
<th class="text-center" style="font-size: 17px;">KIT</th>
<th class="text-center" style="font-size: 17px;">SDS<br /> CONCENTRATION</th>
<th class="text-center" style="font-size: 17px;">NUCLEI<br /> ISOLATION</th>
</tr>
<tr style="background: #fff;">
<td colspan="7"></td>
</tr>
<tr style="background: #fff;">
<td rowspan="5"><img src="https://www.diagenode.com/img/label-histones.png" /></td>
<td class="text-center" style="border-bottom: 1px solid #dedede;">
<div class="label alert" style="font-size: 17px;">CELLS</div>
</td>
<td class="text-center" style="font-size: 17px; border-bottom: 1px solid #dedede;">< 100,000</td>
<td class="text-center" style="font-size: 17px; border-bottom: 1px solid #dedede;"><a href="https://www.diagenode.com/en/p/chromatin-shearing-optimization-kit-high-sds-100-million-cells">Chromatin EasyShear Kit<br />High SDS</a></td>
<td class="text-center" style="font-size: 17px; border-bottom: 1px solid #dedede;">1%</td>
<td class="text-center" style="border-bottom: 1px solid #dedede;"><img src="https://www.diagenode.com/img/cross-unvalid-green.jpg" width="18" height="20" /></td>
</tr>
<tr style="background: #fff; border-bottom: 1px solid #dedede;">
<td class="text-center">
<div class="label alert" style="font-size: 17px;">CELLS</div>
</td>
<td class="text-center" style="font-size: 17px;">> 100,000</td>
<td class="text-center" style="font-size: 17px;"><a href="https://www.diagenode.com/en/p/chromatin-easyshear-kit-ultra-low-sds">Chromatin EasyShear Kit<br />Ultra Low SDS</a></td>
<td class="text-center" style="font-size: 17px;">< 0.1%</td>
<td class="text-center"><img src="https://www.diagenode.com/img/valid.png" width="20" height="16" /></td>
</tr>
<tr style="background: #fff; border-bottom: 1px solid #dedede;">
<td class="text-center">
<div class="label alert" style="font-size: 17px;">TISSUE</div>
</td>
<td class="text-center"></td>
<td class="text-center" style="font-size: 17px;"><a href="https://www.diagenode.com/en/p/chromatin-easyshear-kit-ultra-low-sds">Chromatin EasyShear Kit<br />Ultra Low SDS</a></td>
<td class="text-center" style="font-size: 17px;">< 0.1%</td>
<td class="text-center"><img src="https://www.diagenode.com/img/valid.png" width="20" height="16" /></td>
</tr>
<tr style="background: #fff; border-bottom: 1px solid #dedede;">
<td class="text-center">
<div class="label alert" style="font-size: 17px;">PLANT TISSUE</div>
</td>
<td class="text-center"></td>
<td class="text-center" style="font-size: 17px;"><a href="https://www.diagenode.com/en/p/chromatin-shearing-plant-chip-seq-kit">Chromatin EasyShear Kit<br />for Plant</a></td>
<td class="text-center" style="font-size: 17px;">0.5%</td>
<td class="text-center"><img src="https://www.diagenode.com/img/valid.png" width="20" height="16" /></td>
</tr>
<tr style="background: #fff;">
<td class="text-center">
<div class="label alert" style="font-size: 17px;">FFPE SAMPLES</div>
</td>
<td class="text-center"></td>
<td class="text-center" style="font-size: 17px;"><a href="https://www.diagenode.com/en/p/chromatin-easyshear-kit-low-sds">Chromatin EasyShear Kit<br />Low SDS</a></td>
<td class="text-center" style="font-size: 17px;">0.2%</td>
<td class="text-center"><img src="https://www.diagenode.com/img/valid.png" width="20" height="16" /></td>
</tr>
<tr style="background: #fff;">
<td colspan="7"></td>
</tr>
<tr style="background: #fff;">
<td rowspan="6"><img src="https://www.diagenode.com/img/label-tf.png" /></td>
<td colspan="6"></td>
</tr>
<tr style="background: #fff;">
<td colspan="6"></td>
</tr>
<tr style="background: #fff;">
<td class="text-center">
<div class="label alert" style="font-size: 17px;">CELLS</div>
</td>
<td class="text-center"></td>
<td rowspan="3" class="text-center" style="font-size: 17px;"><a href="https://www.diagenode.com/en/p/chromatin-easyshear-kit-low-sds">Chromatin EasyShear Kit<br />Low SDS</a></td>
<td rowspan="3" class="text-center" style="font-size: 17px;">0.2%</td>
<td rowspan="3" class="text-center"><img src="https://www.diagenode.com/img/valid.png" width="20" height="16" /></td>
</tr>
<tr style="background: #fff;">
<td class="text-center">
<div class="label alert" style="font-size: 17px;">TISSUE</div>
</td>
<td class="text-center"></td>
</tr>
<tr style="background: #fff;">
<td class="text-center">
<div class="label alert" style="font-size: 17px;">FFPE SAMPLES</div>
</td>
<td class="text-center"></td>
</tr>
<tr style="background: #fff;">
<td colspan="6"></td>
</tr>
</tbody>
</table>
<div class="extra-spaced">
<h3>Guide for optimal chromatin preparation using Chromatin EasyShear Kits <i class="fa fa-arrow-circle-right"></i> <a href="https://www.diagenode.com/pages/chromatin-prep-easyshear-kit-guide">Read more</a></h3>
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'description' => '<p><span>The tube holder for 1.5 ml tubes has been especially designed for being used with the <strong>Bioruptor® Pico</strong> and to guarantee homogeneity of chromatin or DNA shearing. It allows for reproducible sonication of up to<strong> 6 x 1.5 ml tubes</strong> at a time with a <strong>sample volume range of 100 to 300 µl</strong>. The holder is made up of a tube holder and its specific dock that makes the sample preparation more ergonomic. <br /></span></p>',
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'description' => '<div class="row">
<div class="small-12 medium-12 large-12 columns">In recent years, advances in Next-Generation Sequencing (NGS) have revolutionized genomics and biology. This growth has fueled demands on upstream techniques for optimal sample preparation and genomic library construction. One of the most critical aspects of optimal library preparation is the quality of the DNA to be sequenced. The DNA must first be effectively and consistently sheared into the appropriate fragment size (depending on the sequencing platform) to enable sensitive and reliable NGS results. The <strong>Bioruptor</strong><sup>®</sup> <strong>Pico</strong> and the <strong>Megaruptor</strong><sup>®</sup> provide superior sample yields, fragment size, and consistency, which are essential for Next-Generation Sequencing workflows. Follow our guidelines and find the good parameters for your expected DNA size: <a href="https://pybrevet.typeform.com/to/o8cQfM">DNA shearing with the Bioruptor<sup>®</sup></a>.</div>
</div>
<p></p>
<div class="row">
<div class="small-7 medium-7 large-7 columns text-center"><img src="https://www.diagenode.com/img/applications/true-flexibility-with-br-ngs.jpg" /></div>
<div class="small-5 medium-5 large-5 columns"><small><strong>Programmable DNA size distribution and high reproducibility with Bioruptor<sup>®</sup> Pico using 0.65 (panel A) or 0.1 ml (panel B) microtubes</strong>. <b>Panel A:</b> 200 bp after 13 cycles (13 sec ON/OFF) using 100 µl volume. Average size: 204; CV%:1.89%). <b>Panel B:</b> 200 bp after 20 cycles (30 sec ON/OFF) using 10 µl volume. (Average size: 215 bp; CV%: 6.6%). <b>Panel A & B:</b> peak electropherogram view. <b>Panel C & D:</b> virtual gel view.</small></div>
</div>
<p><br /><br /></p>
<div class="row">
<div class="small-10 medium-10 large-10 columns text-center end small-offset-1"><img src="https://www.diagenode.com/img/applications/megaruptor-short-frag.jpg" /></div>
<div class="small-12 medium-12 large-12 columns"><small><strong> Reproducible and narrow DNA size distribution with Megaruptor® using short fragment size Hydropores Validation using two different DNA sources and two different methods of analysis. A:</strong> Shearing of lambda phage genomic DNA (20 ng/μl; 150 μl/sample) sheared at different speed settings and analyzed on 1% agarose gel. <strong>B:</strong> Bioanalyzer profiles of human genomic DNA (20 ng/μl; 150 μl/sample) sheared at different software settings of 2 and 5 kb. Three independent experiments were run for each setting. (Agilent DNA 12000 kit was used for separation and fragment sizing).</small></div>
</div>
<p><br /><br /></p>
<div class="row">
<div class="small-4 medium-4 large-4 columns text-center"><img src="https://www.diagenode.com/img/applications/megaruptor-long-frag.jpg" /></div>
<div class="small-8 medium-8 large-8 columns"><small><strong> Demonstrated shearing to fragment sizes between 15 kb and 75 kb with Megaruptor® using long fragment size Hydropores. </strong>Image shows DNA size distribution of human genomic DNA sheared with long fragment Hydropores. DNA was analyzed by pulsed field gel electrophoresis (PFGE) in 1% agarose gel and a mean size of smears was estimated using Image Lab 4.1 software.<br /> * indicates unsheared DNA </small></div>
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'description' => '<div class="row">
<div class="small-12 medium-12 large-12 columns">The most important steps for a successful ChIP include both cell fixation and lysis, and chromatin shearing. Researchers often overlook the critical nature of both of these steps. Eliminating inconsistencies in the shearing step, <strong>Diagenode's Bioruptor</strong><sup>®</sup> uses state-of-the-art ultrasound <strong>ACT</strong> (<strong>A</strong>daptive <strong>C</strong>avitation <strong>T</strong>echnology) to efficiently shear chromatin. ACT enables the highest chromatin quality for high IP efficiency and sensitivity for ChIP experiments with gentle yet highly effective shearing forces. Additionally, the Bioruptor<sup>®</sup> provides a precisely controlled temperature environment that preserves chromatin from heat degradation such that protein-DNA complexes are well-preserved for sensitive, unbiased, and accurate ChIP.<br /><br /> <strong>Diagenode's Bioruptor</strong><sup>®</sup> is the instrument of choice for chromatin shearing used for a number of downstream applications such as qPCR and ChIP-seq that require optimally sheared, unbiased chromatin.</div>
<div class="small-12 medium-12 large-12 columns text-center"><br /><img src="https://www.diagenode.com/img/applications/pico_dna_shearing_fig2.png" /></div>
<div class="small-10 medium-10 large-10 columns end small-offset-1"><small> <br /><strong>Panel A, 10 µl volume:</strong> Chromatin samples are sheared for 10, 20 and 30 cycles of 30 sec ON/30 sec OFF with the Bioruptor® Pico using 0.1 ml Bioruptor® Microtubes (Cat. No. B01200041). <strong>Panel B, 100 µl volume:</strong> Chromatin samples are sheared for 10 cycles of 30 sec ON/30 sec OFF with the Bioruptor® Pico using 0.65 ml Bioruptor® Microtubes (Cat. No. WA-005-0500). <strong>Panel C, 300 µl volume:</strong> Chromatin samples are sheared for 5, 10 and 15 cycles of 30 sec ON/30 sec OFF with the Bioruptor® Pico using using 1.5 ml Bioruptor microtubes (Cat. No. C30010016). Prior to de-crosslinking, samples are treated with RNase cocktail mixture at 37°C during 1 hour. The sheared chromatin is then de-crosslinked overnight and phenol/chloroform purified as described in the kit manual. 10 µl of DNA (equivalent of 500, 000 cells) are analyzed on a 2% agarose gel (MW corresponds to the 100 bp DNA molecular weight marker).</small></div>
<div class="small-12 medium-12 large-12 columns"><br /><br /></div>
<div class="small-12 medium-12 large-12 columns">
<p>It is important to establish optimal conditions to shear crosslinked chromatin to get the correct fragment sizes needed for ChIP. Usually this process requires both optimizing sonication conditions as well as optimizing SDS concentration, which is laborious. With the Chromatin Shearing Optimization Kits, optimization is fast and easy - we provide optimization reagents with varying concentrations of SDS. Moreover, our Chromatin Shearing Optimization Kits can be used for the optimization of chromatin preparation with our kits for ChIP.</p>
</div>
<div class="small-12 medium-12 large-12 columns">
<div class="page" title="Page 7">
<table>
<tbody>
<tr valign="middle">
<td></td>
<td style="text-align: center;"><strong><a href="https://www.diagenode.com/p/chromatin-shearing-optimization-kit-low-sds-100-million-cells">Chromatin Shearing Kit Low SDS (for Histone)</a></strong></td>
<td style="text-align: center;"><strong><a href="https://www.diagenode.com/p/chromatin-shearing-optimization-kit-low-sds-for-tfs-25-rxns">Chromatin Shearing Kit Low SDS (for TF)</a></strong></td>
<td style="text-align: center;"><strong><a href="https://www.diagenode.com/p/chromatin-shearing-optimization-kit-high-sds-100-million-cells">Chromatin Shearing Kit High SDS</a></strong></td>
<td style="text-align: center;"><strong><a href="https://www.diagenode.com/p/chromatin-shearing-optimization-kit-medium-sds-100-million-cells">Chromatin Shearing Kit (for Plant)</a></strong></td>
</tr>
<tr valign="middle" style="background-color: #fff;">
<td>
<p><strong>SDS concentration</strong></p>
</td>
<td style="text-align: center;">
<p>< 0.1%</p>
</td>
<td style="text-align: center;">
<p>0.2%</p>
</td>
<td style="text-align: center;">
<p>1%</p>
</td>
<td style="text-align: center;">
<p>0.5%</p>
</td>
</tr>
<tr valign="middle" style="background-color: #fff;">
<td>
<p><strong>Nuclei isolation</strong></p>
</td>
<td style="text-align: center;">
<p>Yes</p>
</td>
<td style="text-align: center;">
<p>Yes</p>
</td>
<td style="text-align: center;">
<p>No</p>
</td>
<td style="text-align: center;">
<p>Yes</p>
</td>
</tr>
<tr valign="middle" style="background-color: #fff;">
<td>
<p><strong>Allows for shearing of... cells/tissue</strong></p>
</td>
<td style="text-align: center;">
<p>100 million cells</p>
</td>
<td style="text-align: center;">
<p>100 million cells</p>
</td>
<td style="text-align: center;">
<p>100 million cells</p>
</td>
<td style="text-align: center;">
<p>up to 25 g of tissue</p>
</td>
</tr>
<tr valign="middle" style="background-color: #fff;">
<td>
<p><strong>Corresponding to shearing buffers from</strong></p>
</td>
<td style="text-align: center;">
<p><a href="https://www.diagenode.com/en/p/ideal-chip-seq-kit-x24-24-rxns">iDeal ChIP-seq kit for Histones</a></p>
</td>
<td style="text-align: center;">
<p><a href="https://www.diagenode.com/en/p/ideal-chip-seq-kit-for-transcription-factors-x24-24-rxns">iDeal ChIP-seq Kit for Transcription Factors</a></p>
<p><a href="https://www.diagenode.com/en/p/ideal-chip-qpcr-kit">iDeal ChIP qPCR kit</a></p>
</td>
<td style="text-align: center;">
<p><a href="https://www.diagenode.com/en/p/true-microchip-kit-x16-16-rxns">True MicroChIP kit</a></p>
</td>
<td style="text-align: center;">
<p><a href="https://www.diagenode.com/en/p/universal-plant-chip-seq-kit-x24-24-rxns">Universal Plant ChIP-seq kit</a></p>
</td>
</tr>
</tbody>
</table>
<p><em><span style="font-weight: 400;">Table comes from our </span><a href="https://www.diagenode.com/protocols/bioruptor-pico-chromatin-preparation-guide"><span style="font-weight: 400;">Guide for successful chromatin preparation using the Bioruptor® Pico</span></a></em></p>
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<div class="large-12 columns">Diagenode's high yields FFPE DNA extraction using Bioruptor<sup><span>®</span></sup> is a superior method for extracting DNA for Next-Gen Sequencing. Our FFPE DNA Extraction kit contains optimized reagents that are added directly to the FFPE samples to remove paraffin with no toxic reagents, digest tissues, and purify DNA with high yields and low sample degradation. The DNA can then be analyzed by traditional methods or can be sheared with the Bioruptor<sup>®</sup> Pico ultrasonicator for downstream NGS library prep using the MicroPlex Library Preparation Kit.</div>
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<p><span>The 1.5 ml Bioruptor</span><span>® </span><span>Microtubes </span><strong>C30010016 </strong><span>for chromatin shearing strongly improve chromatin sonication efficiency. These tubes have been thoroughly validated for use on the Bioruptor</span><span>® </span><span>Pico (B01060001) and are strongly recommended for DNA and chromatin shearing applications using this instrument. </span></p>
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'description' => '<p><span>HeLa cells are fixed with 1% molecular grade formaldehyde (for 8 min at room temperature). Nucleus isolation is performed using buffers and reagents of Diagenode’s Chromatin Shearing Optimization kit - Low SDS (Cat. No. AA-001-0100) 1x10e6 cells are then resuspended in 100 μl Shearing Buffer prior to chromatin shearing. </span></p>',
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'description' => '<p><span>Therapeutic targeting of the estrogen receptor (ER) is a clinically validated approach for estrogen receptor positive breast cancer (ER+ BC), but sustained response is limited by acquired resistance. Targeting the transcriptional coactivators required for estrogen receptor activity represents an alternative approach that is not subject to the same limitations as targeting estrogen receptor itself. In this report we demonstrate that the acetyltransferase activity of coactivator paralogs CREBBP/EP300 represents a promising therapeutic target in ER+ BC. Using the potent and selective inhibitor CPI-1612, we show that CREBBP/EP300 acetyltransferase inhibition potently suppresses in vitro and in vivo growth of breast cancer cell line models and acts in a manner orthogonal to directly targeting ER. CREBBP/EP300 acetyltransferase inhibition suppresses ER-dependent transcription by targeting lineage-specific enhancers defined by the pioneer transcription factor FOXA1. These results validate CREBBP/EP300 acetyltransferase activity as a viable target for clinical development in ER+ breast cancer.</span></p>',
'date' => '2022-03-30',
'pmid' => 'https://pubmed.ncbi.nlm.nih.gov/35353838/',
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'authors' => 'Bryant, JM and Baumgarten, S and Dingli, F and Loew, D and Sinha, A andClaës, A and Preiser, PR and Dedon, PC and Scherf, A',
'description' => '<p>Mutually exclusive expression of the var multigene family is key to immune evasion and pathogenesis in Plasmodium falciparum, but few factors have been shown to play a direct role. We adapted a CRISPR-based proteomics approach to identify novel factors associated with var genes in their natural chromatin context. Catalytically inactive Cas9 ("dCas9") was targeted to var gene regulatory elements, immunoprecipitated, and analyzed with mass spectrometry. Known and novel factors were enriched including structural proteins, DNA helicases, and chromatin remodelers. Functional characterization of PfISWI, an evolutionarily divergent putative chromatin remodeler enriched at the var gene promoter, revealed a role in transcriptional activation. Proteomics of PfISWI identified several proteins enriched at the var gene promoter such as acetyl-CoA synthetase, a putative MORC protein, and an ApiAP2 transcription factor. These findings validate the CRISPR/dCas9 proteomics method and define a new var gene-associated chromatin complex. This study establishes a tool for targeted chromatin purification of unaltered genomic loci and identifies novel chromatin-associated factors potentially involved in transcriptional control and/or chromatin organization of virulence genes in the human malaria parasite.</p>',
'date' => '2020-08-02',
'pmid' => 'http://www.pubmed.gov/32816370',
'doi' => 'https://dx.doi.org/10.15252%2Fmsb.20209569',
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'authors' => 'Li Y, Dammer EB, Gao Y, Lan Q, Villamil MA, Duong DM, Zhang C, Ping L, Lauinger L, Flick K, Xu Z, Wei W, Xing X, Chang L, Jin J, Hong X, Zhu Y, Wu J, Deng Z, He F, Kaiser P, Xu P',
'description' => '<p>A surprising complexity of ubiquitin signaling has emerged with identification of different ubiquitin chain topologies. However, mechanisms of how the diverse ubiquitin codes control biological processes remain poorly understood. Here, we use quantitative whole-proteome mass spectrometry to identify yeast proteins that are regulated by lysine 11 (K11)-linked ubiquitin chains. The entire Met4 pathway, which links cell proliferation with sulfur amino acid metabolism, was significantly affected by K11 chains and selected for mechanistic studies. Previously, we demonstrated that a K48-linked ubiquitin chain represses the transcription factor Met4. Here, we show that efficient Met4 activation requires a K11-linked topology. Mechanistically, our results propose that the K48 chain binds to a topology-selective tandem ubiquitin binding region in Met4 and competes with binding of the basal transcription machinery to the same region. The change to K11-enriched chain architecture releases this competition and permits binding of the basal transcription complex to activate transcription.</p>',
'date' => '2019-08-06',
'pmid' => 'http://www.pubmed.gov/31444107',
'doi' => '10.1016/j.molcel.2019.07.001',
'modified' => '2019-10-03 09:21:23',
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'name' => 'The role of TCF3 as potential master regulator in blastemal Wilms tumors.',
'authors' => 'Kehl T, Schneider L, Kattler K, Stöckel D, Wegert J, Gerstner N, Ludwig N, Distler U, Tenzer S, Gessler M, Walter J, Keller A, Graf N, Meese E, Lenhof HP',
'description' => '<p>Wilms tumors are the most common type of pediatric kidney tumors. While the overall prognosis for patients is favorable, especially tumors that exhibit a blastemal subtype after preoperative chemotherapy have a poor prognosis. For an improved risk assessment and therapy stratification, it is essential to identify the driving factors that are distinctive for this aggressive subtype. In our study, we compared gene expression profiles of 33 tumor biopsies (17 blastemal and 16 other tumors) after neoadjuvant chemotherapy. The analysis of this dataset using the Regulator Gene Association Enrichment algorithm successfully identified several biomarkers and associated molecular mechanisms that distinguish between blastemal and nonblastemal Wilms tumors. Specifically, regulators involved in embryonic development and epigenetic processes like chromatin remodeling and histone modification play an essential role in blastemal tumors. In this context, we especially identified TCF3 as the central regulatory element. Furthermore, the comparison of ChIP-Seq data of Wilms tumor cell cultures from a blastemal mouse xenograft and a stromal tumor provided further evidence that the chromatin states of blastemal cells share characteristics with embryonic stem cells that are not present in the stromal tumor cell line. These stem-cell like characteristics could potentially add to the increased malignancy and chemoresistance of the blastemal subtype. Along with TCF3, we detected several additional biomarkers that are distinctive for blastemal Wilms tumors after neoadjuvant chemotherapy and that may provide leads for new therapeutic regimens.</p>',
'date' => '2019-03-15',
'pmid' => 'http://www.pubmed.gov/30155889',
'doi' => '10.1002/ijc.31834',
'modified' => '2019-03-21 17:10:17',
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'id' => '3727',
'name' => 'Transcriptome-wide dynamics of extensive m6A mRNA methylation during Plasmodium falciparum blood-stage development',
'authors' => 'Sebastian Baumgarten, Jessica M. Bryant, Ameya Sinha, Thibaud Reyser, Peter R. Preiser, Peter C. Dedon, Artur Scherf',
'description' => '<p>Malaria pathogenesis results from the asexual replication of Plasmodium falciparum within human red blood cells, which relies on a precisely timed cascade of gene expression over a 48-hour life cycle. Although substantial post-transcriptional regulation of this hardwired program has been observed, it remains unclear how these processes are mediated on a transcriptome-wide level. To this end, we identified mRNA modifications in the P. falciparum transcriptome and performed a comprehensive characterization of N6-methyladenosine (m6A) over the course of blood stage development. Using mass spectrometry and m6A RNA sequencing, we demonstrate that m6A is highly developmentally regulated, exceeding m6A levels known in any other eukaryote. We identify an evolutionarily conserved m6A writer complex and show that knockdown of the putative m6A methyltransferase by CRISPR interference leads to increased levels of transcripts that normally contain m6A. In accordance, we find an inverse correlation between m6A status and mRNA stability or translational efficiency. Our data reveal the crucial role of extensive m6A mRNA methylation in dynamically fine-tuning the transcriptional program of a unicellular eukaryote as well as a new ‘epitranscriptomic’ layer of gene regulation in malaria parasites.</p>',
'date' => '2019-03-09',
'pmid' => 'https://www.nature.com/articles/s41564-019-0521-7',
'doi' => '10.1101/572891.',
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'name' => 'Dot1 promotes H2B ubiquitination by a methyltransferase-independent mechanism.',
'authors' => 'van Welsem T, Korthout T, Ekkebus R, Morais D, Molenaar TM, van Harten K, Poramba-Liyanage DW, Sun SM, Lenstra TL, Srivas R, Ideker T, Holstege FCP, van Attikum H, El Oualid F, Ovaa H, Stulemeijer IJE, Vlaming H, van Leeuwen F',
'description' => '<p>The histone methyltransferase Dot1 is conserved from yeast to human and methylates lysine 79 of histone H3 (H3K79) on the core of the nucleosome. H3K79 methylation by Dot1 affects gene expression and the response to DNA damage, and is enhanced by monoubiquitination of the C-terminus of histone H2B (H2Bub1). To gain more insight into the functions of Dot1, we generated genetic interaction maps of increased-dosage alleles of DOT1. We identified a functional relationship between increased Dot1 dosage and loss of the DUB module of the SAGA co-activator complex, which deubiquitinates H2Bub1 and thereby negatively regulates H3K79 methylation. Increased Dot1 dosage was found to promote H2Bub1 in a dose-dependent manner and this was exacerbated by the loss of SAGA-DUB activity, which also caused a negative genetic interaction. The stimulatory effect on H2B ubiquitination was mediated by the N-terminus of Dot1, independent of methyltransferase activity. Our findings show that Dot1 and H2Bub1 are subject to bi-directional crosstalk and that Dot1 possesses chromatin regulatory functions that are independent of its methyltransferase activity.</p>',
'date' => '2018-09-08',
'pmid' => 'http://www.pubmed.gov/30203048',
'doi' => '10.1093/nar/gky801',
'modified' => '2018-11-09 12:13:19',
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'name' => 'BET protein inhibition sensitizes glioblastoma cells to temozolomidetreatment by attenuating MGMT expression',
'authors' => 'Tancredi A. et al.',
'description' => '<p>Bromodomain and extra-terminal tail (BET) proteins have been identified as potential epigenetic targets in cancer, including glioblastoma. These epigenetic modifiers link the histone code to gene transcription that can be disrupted with small molecule BET inhibitors (BETi). With the aim of developing rational combination treatments for glioblastoma, we analyzed BETi-induced differential gene expression in glioblastoma derived-spheres, and identified 6 distinct response patterns. To uncover emerging actionable vulnerabilities that can be targeted with a second drug, we extracted the 169 significantly disturbed DNA Damage Response genes and inspected their response pattern. The most prominent candidate with consistent downregulation, was the O-6-methylguanine-DNA methyltransferase (MGMT) gene, a known resistance factor for alkylating agent therapy in glioblastoma. BETi not only reduced MGMT expression in GBM cells, but also inhibited its induction, typically observed upon temozolomide treatment. To determine the potential clinical relevance, we evaluated the specificity of the effect on MGMT expression and MGMT mediated treatment resistance to temozolomide. BETi-mediated attenuation of MGMT expression was associated with reduction of BRD4- and Pol II-binding at the MGMT promoter. On the functional level, we demonstrated that ectopic expression of MGMT under an unrelated promoter was not affected by BETi, while under the same conditions, pharmacologic inhibition of MGMT restored the sensitivity to temozolomide, reflected in an increased level of g-H2AX, a proxy for DNA double-strand breaks. Importantly, expression of MSH6 and MSH2, which are required for sensitivity to unrepaired O6-methylGuanin-lesions, was only briefly affected by BETi. Taken together, the addition of BET-inhibitors to the current standard of care, comprising temozolomide treatment, may sensitize the 50\% of patients whose glioblastoma exert an unmethylated MGMT promoter.</p>',
'date' => '0000-00-00',
'pmid' => 'https://www.researchsquare.com/article/rs-1832996/v1',
'doi' => '10.21203/rs.3.rs-1832996/v1',
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</div>
</div>
<form action="/jp/quotes/quote?id=3046" id="Quote-3046" class="quote" method="post" accept-charset="utf-8"><div style="display:none;"><input type="hidden" name="_method" value="POST"/></div><input type="hidden" name="data[Quote][product_id]" value="3046" id="QuoteProductId"/><input type="hidden" name="data[Quote][formLoaded6tY4bPYk]" value="S0dDZmdsL0JmY0M2WW5zUkkvYldzZz09" id="QuoteFormLoaded6tY4bPYk"/><input type="hidden" name="data[Quote][product_rfq_tag]" value="bioruptorpico2" id="QuoteProductRfqTag"/><input type="hidden" name="data[Quote][source_quote]" value="modal quote" id="QuoteSourceQuote"/>
<div class="row collapse">
<h2>Contact Information</h2>
<div class="small-3 large-2 columns">
<span class="prefix">First name <sup style="font-size:16px;color:red;">*</sup></span>
</div>
<div class="small-9 large-10 columns">
<input name="data[Quote][first_name]" placeholder="john" maxlength="255" type="text" id="QuoteFirstName" required="required"/> </div>
</div>
<div class="row collapse">
<div class="small-3 large-2 columns">
<span class="prefix">Last name <sup style="font-size:16px;color:red;">*</sup></span>
</div>
<div class="small-9 large-10 columns">
<input name="data[Quote][last_name]" placeholder="doe" maxlength="255" type="text" id="QuoteLastName" required="required"/> </div>
</div>
<div class="row collapse">
<div class="small-3 large-2 columns">
<span class="prefix">Company <sup style="font-size:16px;color:red;">*</sup></span>
</div>
<div class="small-9 large-10 columns">
<input name="data[Quote][company]" placeholder="Organisation / Institute" maxlength="255" type="text" id="QuoteCompany" required="required"/> </div>
</div>
<div class="row collapse">
<div class="small-3 large-2 columns">
<span class="prefix">Phone number</span>
</div>
<div class="small-9 large-10 columns">
<input name="data[Quote][phone_number]" placeholder="+1 862 209-4680" maxlength="255" type="text" id="QuotePhoneNumber"/> </div>
</div>
<div class="row collapse">
<div class="small-3 large-2 columns">
<span class="prefix">City</span>
</div>
<div class="small-9 large-10 columns">
<input name="data[Quote][city]" placeholder="Denville" maxlength="255" type="text" id="QuoteCity"/> </div>
</div>
<div class="row collapse">
<div class="small-3 large-2 columns">
<span class="prefix">Country <sup style="font-size:16px;color:red;">*</sup></span>
</div>
<div class="small-9 large-10 columns">
<select name="data[Quote][country]" required="required" class="triggers" id="country_selector_quote-3046">
<option value="">-- select a country --</option>
<option value="AF">Afghanistan</option>
<option value="AX">Åland Islands</option>
<option value="AL">Albania</option>
<option value="DZ">Algeria</option>
<option value="AS">American Samoa</option>
<option value="AD">Andorra</option>
<option value="AO">Angola</option>
<option value="AI">Anguilla</option>
<option value="AQ">Antarctica</option>
<option value="AG">Antigua and Barbuda</option>
<option value="AR">Argentina</option>
<option value="AM">Armenia</option>
<option value="AW">Aruba</option>
<option value="AU">Australia</option>
<option value="AT">Austria</option>
<option value="AZ">Azerbaijan</option>
<option value="BS">Bahamas</option>
<option value="BH">Bahrain</option>
<option value="BD">Bangladesh</option>
<option value="BB">Barbados</option>
<option value="BY">Belarus</option>
<option value="BE">Belgium</option>
<option value="BZ">Belize</option>
<option value="BJ">Benin</option>
<option value="BM">Bermuda</option>
<option value="BT">Bhutan</option>
<option value="BO">Bolivia</option>
<option value="BQ">Bonaire, Sint Eustatius and Saba</option>
<option value="BA">Bosnia and Herzegovina</option>
<option value="BW">Botswana</option>
<option value="BV">Bouvet Island</option>
<option value="BR">Brazil</option>
<option value="IO">British Indian Ocean Territory</option>
<option value="BN">Brunei Darussalam</option>
<option value="BG">Bulgaria</option>
<option value="BF">Burkina Faso</option>
<option value="BI">Burundi</option>
<option value="KH">Cambodia</option>
<option value="CM">Cameroon</option>
<option value="CA">Canada</option>
<option value="CV">Cape Verde</option>
<option value="KY">Cayman Islands</option>
<option value="CF">Central African Republic</option>
<option value="TD">Chad</option>
<option value="CL">Chile</option>
<option value="CN">China</option>
<option value="CX">Christmas Island</option>
<option value="CC">Cocos (Keeling) Islands</option>
<option value="CO">Colombia</option>
<option value="KM">Comoros</option>
<option value="CG">Congo</option>
<option value="CD">Congo, The Democratic Republic of the</option>
<option value="CK">Cook Islands</option>
<option value="CR">Costa Rica</option>
<option value="CI">Côte d'Ivoire</option>
<option value="HR">Croatia</option>
<option value="CU">Cuba</option>
<option value="CW">Curaçao</option>
<option value="CY">Cyprus</option>
<option value="CZ">Czech Republic</option>
<option value="DK">Denmark</option>
<option value="DJ">Djibouti</option>
<option value="DM">Dominica</option>
<option value="DO">Dominican Republic</option>
<option value="EC">Ecuador</option>
<option value="EG">Egypt</option>
<option value="SV">El Salvador</option>
<option value="GQ">Equatorial Guinea</option>
<option value="ER">Eritrea</option>
<option value="EE">Estonia</option>
<option value="ET">Ethiopia</option>
<option value="FK">Falkland Islands (Malvinas)</option>
<option value="FO">Faroe Islands</option>
<option value="FJ">Fiji</option>
<option value="FI">Finland</option>
<option value="FR">France</option>
<option value="GF">French Guiana</option>
<option value="PF">French Polynesia</option>
<option value="TF">French Southern Territories</option>
<option value="GA">Gabon</option>
<option value="GM">Gambia</option>
<option value="GE">Georgia</option>
<option value="DE">Germany</option>
<option value="GH">Ghana</option>
<option value="GI">Gibraltar</option>
<option value="GR">Greece</option>
<option value="GL">Greenland</option>
<option value="GD">Grenada</option>
<option value="GP">Guadeloupe</option>
<option value="GU">Guam</option>
<option value="GT">Guatemala</option>
<option value="GG">Guernsey</option>
<option value="GN">Guinea</option>
<option value="GW">Guinea-Bissau</option>
<option value="GY">Guyana</option>
<option value="HT">Haiti</option>
<option value="HM">Heard Island and McDonald Islands</option>
<option value="VA">Holy See (Vatican City State)</option>
<option value="HN">Honduras</option>
<option value="HK">Hong Kong</option>
<option value="HU">Hungary</option>
<option value="IS">Iceland</option>
<option value="IN">India</option>
<option value="ID">Indonesia</option>
<option value="IR">Iran, Islamic Republic of</option>
<option value="IQ">Iraq</option>
<option value="IE">Ireland</option>
<option value="IM">Isle of Man</option>
<option value="IL">Israel</option>
<option value="IT">Italy</option>
<option value="JM">Jamaica</option>
<option value="JP">Japan</option>
<option value="JE">Jersey</option>
<option value="JO">Jordan</option>
<option value="KZ">Kazakhstan</option>
<option value="KE">Kenya</option>
<option value="KI">Kiribati</option>
<option value="KP">Korea, Democratic People's Republic of</option>
<option value="KR">Korea, Republic of</option>
<option value="KW">Kuwait</option>
<option value="KG">Kyrgyzstan</option>
<option value="LA">Lao People's Democratic Republic</option>
<option value="LV">Latvia</option>
<option value="LB">Lebanon</option>
<option value="LS">Lesotho</option>
<option value="LR">Liberia</option>
<option value="LY">Libya</option>
<option value="LI">Liechtenstein</option>
<option value="LT">Lithuania</option>
<option value="LU">Luxembourg</option>
<option value="MO">Macao</option>
<option value="MK">Macedonia, Republic of</option>
<option value="MG">Madagascar</option>
<option value="MW">Malawi</option>
<option value="MY">Malaysia</option>
<option value="MV">Maldives</option>
<option value="ML">Mali</option>
<option value="MT">Malta</option>
<option value="MH">Marshall Islands</option>
<option value="MQ">Martinique</option>
<option value="MR">Mauritania</option>
<option value="MU">Mauritius</option>
<option value="YT">Mayotte</option>
<option value="MX">Mexico</option>
<option value="FM">Micronesia, Federated States of</option>
<option value="MD">Moldova</option>
<option value="MC">Monaco</option>
<option value="MN">Mongolia</option>
<option value="ME">Montenegro</option>
<option value="MS">Montserrat</option>
<option value="MA">Morocco</option>
<option value="MZ">Mozambique</option>
<option value="MM">Myanmar</option>
<option value="NA">Namibia</option>
<option value="NR">Nauru</option>
<option value="NP">Nepal</option>
<option value="NL">Netherlands</option>
<option value="NC">New Caledonia</option>
<option value="NZ">New Zealand</option>
<option value="NI">Nicaragua</option>
<option value="NE">Niger</option>
<option value="NG">Nigeria</option>
<option value="NU">Niue</option>
<option value="NF">Norfolk Island</option>
<option value="MP">Northern Mariana Islands</option>
<option value="NO">Norway</option>
<option value="OM">Oman</option>
<option value="PK">Pakistan</option>
<option value="PW">Palau</option>
<option value="PS">Palestine, State of</option>
<option value="PA">Panama</option>
<option value="PG">Papua New Guinea</option>
<option value="PY">Paraguay</option>
<option value="PE">Peru</option>
<option value="PH">Philippines</option>
<option value="PN">Pitcairn</option>
<option value="PL">Poland</option>
<option value="PT">Portugal</option>
<option value="PR">Puerto Rico</option>
<option value="QA">Qatar</option>
<option value="RE">Réunion</option>
<option value="RO">Romania</option>
<option value="RU">Russian Federation</option>
<option value="RW">Rwanda</option>
<option value="BL">Saint Barthélemy</option>
<option value="SH">Saint Helena, Ascension and Tristan da Cunha</option>
<option value="KN">Saint Kitts and Nevis</option>
<option value="LC">Saint Lucia</option>
<option value="MF">Saint Martin (French part)</option>
<option value="PM">Saint Pierre and Miquelon</option>
<option value="VC">Saint Vincent and the Grenadines</option>
<option value="WS">Samoa</option>
<option value="SM">San Marino</option>
<option value="ST">Sao Tome and Principe</option>
<option value="SA">Saudi Arabia</option>
<option value="SN">Senegal</option>
<option value="RS">Serbia</option>
<option value="SC">Seychelles</option>
<option value="SL">Sierra Leone</option>
<option value="SG">Singapore</option>
<option value="SX">Sint Maarten (Dutch part)</option>
<option value="SK">Slovakia</option>
<option value="SI">Slovenia</option>
<option value="SB">Solomon Islands</option>
<option value="SO">Somalia</option>
<option value="ZA">South Africa</option>
<option value="GS">South Georgia and the South Sandwich Islands</option>
<option value="ES">Spain</option>
<option value="LK">Sri Lanka</option>
<option value="SD">Sudan</option>
<option value="SR">Suriname</option>
<option value="SS">South Sudan</option>
<option value="SJ">Svalbard and Jan Mayen</option>
<option value="SZ">Swaziland</option>
<option value="SE">Sweden</option>
<option value="CH">Switzerland</option>
<option value="SY">Syrian Arab Republic</option>
<option value="TW">Taiwan</option>
<option value="TJ">Tajikistan</option>
<option value="TZ">Tanzania</option>
<option value="TH">Thailand</option>
<option value="TL">Timor-Leste</option>
<option value="TG">Togo</option>
<option value="TK">Tokelau</option>
<option value="TO">Tonga</option>
<option value="TT">Trinidad and Tobago</option>
<option value="TN">Tunisia</option>
<option value="TR">Turkey</option>
<option value="TM">Turkmenistan</option>
<option value="TC">Turks and Caicos Islands</option>
<option value="TV">Tuvalu</option>
<option value="UG">Uganda</option>
<option value="UA">Ukraine</option>
<option value="AE">United Arab Emirates</option>
<option value="GB">United Kingdom</option>
<option value="US" selected="selected">United States</option>
<option value="UM">United States Minor Outlying Islands</option>
<option value="UY">Uruguay</option>
<option value="UZ">Uzbekistan</option>
<option value="VU">Vanuatu</option>
<option value="VE">Venezuela</option>
<option value="VN">Viet Nam</option>
<option value="VG">Virgin Islands, British</option>
<option value="VI">Virgin Islands, U.S.</option>
<option value="WF">Wallis and Futuna</option>
<option value="EH">Western Sahara</option>
<option value="YE">Yemen</option>
<option value="ZM">Zambia</option>
<option value="ZW">Zimbabwe</option>
</select><script>
$('#country_selector_quote-3046').selectize();
</script><br />
</div>
</div>
<div class="row collapse">
<div class="small-3 large-2 columns">
<span class="prefix">State</span>
</div>
<div class="small-9 large-10 columns">
<input name="data[Quote][state]" id="state-3046" maxlength="3" type="text"/><br />
</div>
</div>
<div class="row collapse">
<div class="small-3 large-2 columns">
<span class="prefix">Email <sup style="font-size:16px;color:red;">*</sup></span>
</div>
<div class="small-9 large-10 columns">
<input name="data[Quote][email]" placeholder="email@address.com" maxlength="255" type="email" id="QuoteEmail" required="required"/> </div>
</div>
<div class="row collapse" id="email_v">
<div class="small-3 large-2 columns">
<span class="prefix">Email verification<sup style="font-size:16px;color:red;">*</sup></span>
</div>
<div class="small-9 large-10 columns">
<input name="data[Quote][email_v]" autocomplete="nope" type="text" id="QuoteEmailV"/> </div>
</div>
<div class="row collapse">
<div class="small-3 large-2 columns">
<span class="prefix">Comment</span>
</div>
<div class="small-9 large-10 columns">
<textarea name="data[Quote][comment]" placeholder="Additional comments" cols="30" rows="6" id="QuoteComment"></textarea> </div>
</div>
<!------------SERVICES PARTICULAR FORM START---------------->
<!------------DATA TO POPULATE REGARDING SPECIFIC SERVICES----->
<div class="row collapse">
<div class="small-3 large-2 columns">
</div>
<div class="small-9 large-10 columns">
<div class="recaptcha"><div id="recaptcha662a951ce5b49"></div></div> </div>
</div>
<br />
<div class="row collapse">
<div class="small-3 large-2 columns">
</div>
<div class="small-9 large-10 columns">
<button id="submit_btn-3046" class="alert button expand" form="Quote-3046" type="submit">Contact me</button> </div>
</div>
</form><script>
var pardotFormHandlerURL = 'https://go.diagenode.com/l/928883/2022-10-10/36b1c';
function postToPardot(formAction, id) {
$('#pardot-form-handler').load(function(){
$('#Quote-' + id).attr('action', formAction);
$('#Quote-' + id).submit();
});
$('#pardot-form-handler').attr('src', pardotFormHandlerURL + '?' + $('#Quote-' + id).serialize());
}
$(document).ready(function() {
$('body').append('<iframe id="pardot-form-handler" height="0" width="0" style="position:absolute; left:-100000px; top:-100000px" src="javascript:false;"></iframe>');
$('#Quote-3046').attr('action','javascript:postToPardot(\'' + $('#Quote-3046').attr('action') + '\', 3046)');
});
$("#Quote-3046 #submit_btn-3046").click(function (e) {
if($(this).closest('form')[0].checkValidity()){
e.preventDefault();
//disable the submit button
$("#Quote-3046 #submit_btn-3046").attr("disabled", true);
$("#Quote-3046 #submit_btn-3046").html("Processing...");
//submit the form
$("#Quote-3046").submit();
}
})
</script>
<script>
if ($("#Quote-3046 #country_selector_quote-3046.selectized").val() == 'US') {
var val = $("#state-3046").val();
$("#Quote-3046 #state-3046").replaceWith('<select name="data[Quote][state]" id="state-3046" required><option disabled selected value> -- select a state -- </option><option value="AL">Alabama (AL)</option><option value="AK">Alaska (AK)</option><option value="AZ">Arizona (AZ)</option><option value="AR">Arkansas (AR)</option><option value="CA">California (CA)</option><option value="CO">Colorado (CO)</option><option value="CT">Connecticut (CT)</option><option value="DE">Delaware (DE)</option><option value="FL">Florida (FL)</option><option value="GA">Georgia (GA)</option><option value="HI">Hawaii (HI)</option><option value="ID">Idaho (ID)</option><option value="IL">Illinois (IL)</option><option value="IN">Indiana (IN)</option><option value="IA">Iowa (IA)</option><option value="KS">Kansas (KS)</option><option value="KY">Kentucky (KY)</option><option value="LA">Louisiana (LA)</option><option value="ME">Maine (ME)</option><option value="MD">Maryland (MD)</option><option value="MA">Massachusetts (MA)</option><option value="MI">Michigan (MI)</option><option value="MN">Minnesota (MN)</option><option value="MS">Mississippi (MS)</option><option value="MO">Missouri (MO)</option><option value="MT">Montana (MT)</option><option value="NE">Nebraska (NE)</option><option value="NV">Nevada (NV)</option><option value="NH">New Hampshire (NH)</option><option value="NJ">New Jersey (NJ)</option><option value="NM">New Mexico (NM)</option><option value="NY">New York (NY)</option><option value="NC">North Carolina (NC)</option><option value="ND">North Dakota (ND)</option><option value="OH">Ohio (OH)</option><option value="OK">Oklahoma (OK)</option><option value="OR">Oregon (OR)</option><option value="PA">Pennsylvania (PA)</option><option value="PR">Puerto Rico (PR)</option><option value="RI">Rhode Island (RI)</option><option value="SC">South Carolina (SC)</option><option value="SD">South Dakota (SD)</option><option value="TN">Tennessee (TN)</option><option value="TX">Texas (TX)</option><option value="UT">Utah (UT)</option><option value="VT">Vermont (VT)</option><option value="VA">Virginia (VA)</option><option value="WA">Washington (WA)</option><option value="WV">West Virginia (WV)</option><option value="WI">Wisconsin (WI)</option><option value="WY">Wyoming (WY)</option><option value="DC">District of Columbia (DC)</option><option value="AS">American Samoa (AS)</option><option value="GU">Guam (GU)</option><option value="MP">Northern Mariana Islands (MP)</option><option value="PR">Puerto Rico (PR)</option><option value="UM">United States Minor Outlying Islands (UM)</option><option value="VI">Virgin Islands (VI)</option></select>');
if (val.length == 2) {
$("#state-3046").val(val);
}
$("#state-3046").parent().parent().show();
} else if ($("#Quote-3046 #country_selector_quote-3046.selectized").val() == 'CA') {
var val = $("#state-3046").val();
$("#Quote-3046 #state-3046").replaceWith('<select name="data[Quote][state]" id="state-3046" required><option disabled selected value> -- select a state -- </option><option value="AB">Alberta (AB)</option><option value="BC">British Columbia (BC)</option><option value="MB">Manitoba (MB)</option><option value="NB">New Brunswick (NB)</option><option value="NL">Newfoundland and Labrador (NL)</option><option value="NS">Nova Scotia (NS)</option><option value="ON">Ontario (ON)</option><option value="PE">Prince Edward Island (PE)</option><option value="QC">Quebec (QC)</option><option value="SK">Saskatchewan (SK)</option></select>');
if (val.length == 2) {
$("#state-3046").val(val);
}
$("#state-3046").parent().parent().show();
} else if ($("#Quote-3046 #country_selector_quote-3046.selectized").val() == 'DE') {
var val = $("#state-3046").val();
$("#Quote-3046 #state-3046").replaceWith('<select name="data[Quote][state]" id="state-3046" required><option disabled selected value> -- select a state -- </option><option value="BW">Baden-Württemberg (BW)</option><option value="BY">Bayern (BY)</option><option value="BE">Berlin (BE)</option><option value="BB">Brandeburg (BB)</option><option value="HB">Bremen (HB)</option><option value="HH">Hamburg (HH)</option><option value="HE">Hessen (HE)</option><option value="MV">Mecklenburg-Vorpommern (MV)</option><option value="NI">Niedersachsen (NI)</option><option value="NW">Nordrhein-Westfalen (NW)</option><option value="RP">Rheinland-Pfalz (RP)</option><option value="SL">Saarland (SL)</option><option value="SN">Sachsen (SN)</option><option value ="SA">Sachsen-Anhalt (SA)</option><option value="SH">Schleswig-Holstein (SH)</option><option value="TH">Thüringen</option></select>');
if (val.length == 2) {
$("#state-3046").val(val);
}
$("#state-3046").parent().parent().show();
} else {
$("#Quote-3046 #state-3046").parent().parent().hide();
$("#Quote-3046 #state-3046").replaceWith('<input name="data[Quote][state]" maxlength="255" type="text" id="state-3046" value="">');
}
$("#Quote-3046 #country_selector_quote-3046.selectized").change(function() {
if (this.value == 'US') {
$("#Quote-3046 #state-3046").replaceWith('<select name="data[Quote][state]" id="state-3046" required><option disabled selected value> -- select a state -- </option><option value="AL">Alabama (AL)</option><option value="AK">Alaska (AK)</option><option value="AZ">Arizona (AZ)</option><option value="AR">Arkansas (AR)</option><option value="CA">California (CA)</option><option value="CO">Colorado (CO)</option><option value="CT">Connecticut (CT)</option><option value="DE">Delaware (DE)</option><option value="FL">Florida (FL)</option><option value="GA">Georgia (GA)</option><option value="HI">Hawaii (HI)</option><option value="ID">Idaho (ID)</option><option value="IL">Illinois (IL)</option><option value="IN">Indiana (IN)</option><option value="IA">Iowa (IA)</option><option value="KS">Kansas (KS)</option><option value="KY">Kentucky (KY)</option><option value="LA">Louisiana (LA)</option><option value="ME">Maine (ME)</option><option value="MD">Maryland (MD)</option><option value="MA">Massachusetts (MA)</option><option value="MI">Michigan (MI)</option><option value="MN">Minnesota (MN)</option><option value="MS">Mississippi (MS)</option><option value="MO">Missouri (MO)</option><option value="MT">Montana (MT)</option><option value="NE">Nebraska (NE)</option><option value="NV">Nevada (NV)</option><option value="NH">New Hampshire (NH)</option><option value="NJ">New Jersey (NJ)</option><option value="NM">New Mexico (NM)</option><option value="NY">New York (NY)</option><option value="NC">North Carolina (NC)</option><option value="ND">North Dakota (ND)</option><option value="OH">Ohio (OH)</option><option value="OK">Oklahoma (OK)</option><option value="OR">Oregon (OR)</option><option value="PA">Pennsylvania (PA)</option><option value="PR">Puerto Rico (PR)</option><option value="RI">Rhode Island (RI)</option><option value="SC">South Carolina (SC)</option><option value="SD">South Dakota (SD)</option><option value="TN">Tennessee (TN)</option><option value="TX">Texas (TX)</option><option value="UT">Utah (UT)</option><option value="VT">Vermont (VT)</option><option value="VA">Virginia (VA)</option><option value="WA">Washington (WA)</option><option value="WV">West Virginia (WV)</option><option value="WI">Wisconsin (WI)</option><option value="WY">Wyoming (WY)</option><option value="DC">District of Columbia (DC)</option><option value="AS">American Samoa (AS)</option><option value="GU">Guam (GU)</option><option value="MP">Northern Mariana Islands (MP)</option><option value="PR">Puerto Rico (PR)</option><option value="UM">United States Minor Outlying Islands (UM)</option><option value="VI">Virgin Islands (VI)</option></select>');
$("#Quote-3046 #state-3046").parent().parent().show();
} else if (this.value == 'CA') {
$("#Quote-3046 #state-3046").replaceWith('<select name="data[Quote][state]" id="state-3046" required><option disabled selected value> -- select a state -- </option><option value="AB">Alberta (AB)</option><option value="BC">British Columbia (BC)</option><option value="MB">Manitoba (MB)</option><option value="NB">New Brunswick (NB)</option><option value="NL">Newfoundland and Labrador (NL)</option><option value="NS">Nova Scotia (NS)</option><option value="ON">Ontario (ON)</option><option value="PE">Prince Edward Island (PE)</option><option value="QC">Quebec (QC)</option><option value="SK">Saskatchewan (SK)</option></select>');
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<h6 style="height:60px">Picoruptor 2 sonication device </h6>
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'name' => 'Bioruptor<sup>®</sup> Pico sonication device',
'description' => '<p><a href="https://go.diagenode.com/bioruptor-upgrade"><img src="https://www.diagenode.com/img/banners/banner-br-trade.png" /></a></p>
<p><a href="https://www.diagenode.com/en/categories/bioruptor-maintenance"><img src="https://www.diagenode.com/img/banners/maintenance-banner-br.png" /></a></p>
<div class="row">
<div class="small-12 medium-8 large-8 columns"><br />
<p><span>The Bioruptor® Pico is the latest innovation in shearing and represents a new breakthrough as an all-in-one shearing system capable of shearing samples from 150 bp to 1 kb. </span>Since 2004, Diagenode has accumulated <strong>shearing expertise</strong> to design the Bioruptor® Pico and guarantee the best experience with the <strong>sample preparation</strong> for <strong>number of applications -- in various fields of studies</strong> including environmental research, toxicology, genomics and epigenomics, cancer research, stem cells and development, neuroscience, clinical applications, agriculture, and many more.</p>
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<p>The Bioruptor Pico shearing accessories and consumables have been developed to allow <strong>flexibility in sample volumes</strong> (20 µl - 2 ml) and a <strong>fast parallel processing of samples</strong> (up to 16 samples simultaneously). <span>The built-in cooling system (Bioruptor® Cooler) ensures high precision <strong>temperature control</strong>. The <strong>user-friendly interface</strong> has been designed for any researcher, providing an easy and advanced modes that give both beginners and experienced users the right level of control. </span></p>
<p>In addition, Diagenode provides fully-validated tubes that remain <strong>budget-friendly with low operating cost</strong> (< 1€/$/DNA sample) and shearing kits for best sample quality. <span></span></p>
<p><strong>Application versatility</strong>:</p>
<ul>
<li>DNA shearing for Next-Generation-Sequencing</li>
<li>Chromatin shearing</li>
<li>RNA shearing</li>
<li>Protein extraction from tissues and cells (also for mass spectrometry)</li>
<li>FFPE DNA extraction</li>
<li>Protein aggregation studies</li>
<li>CUT&RUN - shearing of input DNA for NGS</li>
</ul>
<div style="background-color: #f1f3f4; margin: 10px; padding: 50px;">
<p><strong>Bioruptor Pico: Recommended for CUT&RUN sequencing for input DNA</strong><br /><br /> By combining antibody-targeted controlled cleavage by MNase and NGS, <strong>CUT&RUN sequencing</strong> can be used to identify protein-DNA binding sites genome-wide. CUT&RUN works by using the DNA cleaving activity of a Protein A-fused MNase to isolate DNA that is bound by a protein of interest. This targeted digestion is controlled by the addition of calcium, which MNase requires for its nuclease activity. After MNase digestion, short DNA fragments are released and can then be purified for subsequent library preparation and high-throughput sequencing. While CUT&RUN does not require mechanical shearing chromatin given the enzymatic approach, sonication is highly recommended for the fragmentation of the input DNA (used to compare the enriched sample) in order to be compatible with downstream NGS. The Bioruptor Pico is the ideal instrument of choice for generating optimal DNA fragments with a tight distribution, assuring excellent library prep and excellent sequencing results for your CUT&RUN assay.<br /><br /> <strong>Explore the Bioruptor Pico now.</strong></p>
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<div class="extra-spaced"><img alt="Bioruptor Sonication for DNA shearing for Next-Generation-Sequencing" src="https://www.diagenode.com/img/product/shearing_technologies/guarantie.png" /></div>
<div class="extra-spaced"><center><img alt="Bioruptor Sonication for Chromatin shearing" src="https://www.diagenode.com/img/product/shearing_technologies/pico-reproducibility-is-priority.jpg" /></center></div>
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'label2' => 'View accessories & consumables for Bioruptor<sup>®</sup> Pico',
'info2' => '<h3>Shearing Accessories</h3>
<table style="width: 641px;">
<thead>
<tr style="background-color: #dddddd; height: 37px;">
<td style="width: 300px; height: 37px;"><strong>Name</strong></td>
<td style="width: 171px; text-align: center; height: 37px;">Catalog number</td>
<td style="width: 160px; text-align: center; height: 37px;">Throughput</td>
</tr>
</thead>
<tbody>
<tr style="height: 38px;">
<td style="width: 300px; height: 38px;"><a href="https://www.diagenode.com/en/p/0-2-ml-tube-holder-dock-for-bioruptor-pico">Tube holder for 0.2 ml tubes</a></td>
<td style="width: 171px; text-align: center; height: 38px;"><span style="font-weight: 400;">B01201144</span></td>
<td style="width: 160px; text-align: center; height: 38px;"><span style="font-weight: 400;">16 samples</span></td>
</tr>
<tr style="height: 38px;">
<td style="width: 300px; height: 38px;"><a href="https://www.diagenode.com/en/p/0-65-ml-tube-holder-dock-for-bioruptor-pico">Tube holder for 0.65 ml tubes</a></td>
<td style="width: 171px; text-align: center; height: 38px;"><span style="font-weight: 400;">B01201143</span></td>
<td style="width: 160px; text-align: center; height: 38px;"><span style="font-weight: 400;">12 samples<br /></span></td>
</tr>
<tr style="height: 38px;">
<td style="width: 300px; height: 38px;"><a href="https://www.diagenode.com/en/p/1-5-ml-tube-holder-dock-for-bioruptor-pico">Tube holder for 1.5 ml tubes</a></td>
<td style="width: 171px; text-align: center; height: 38px;"><span style="font-weight: 400;">B01201140</span></td>
<td style="width: 160px; text-align: center; height: 38px;"><span style="font-weight: 400;">6 samples<br /></span></td>
</tr>
<tr style="height: 37px;">
<td style="width: 300px; height: 37px;"><a href="https://www.diagenode.com/en/p/15-ml-sonication-accessories-for-bioruptor-standard-plus-pico-1-pack">15 ml sonication accessories</a></td>
<td style="width: 171px; text-align: center; height: 37px;"><span style="font-weight: 400;">B01200016</span></td>
<td style="width: 160px; text-align: center; height: 37px;"><span style="font-weight: 400;">6 samples<br /></span></td>
</tr>
</tbody>
</table>
<h3>Shearing Consumables</h3>
<table style="width: 646px;">
<thead>
<tr style="background-color: #dddddd; height: 37px;">
<td style="width: 286px; height: 37px;"><strong>Name</strong></td>
<td style="width: 76px; height: 37px; text-align: center;">Catalog Number</td>
</tr>
</thead>
<tbody>
<tr style="height: 37px;">
<td style="width: 286px; height: 37px;"><a href="https://www.diagenode.com/en/p/02ml-microtubes-for-bioruptor-pico">0.2 ml Pico Microtubes</a></td>
<td style="width: 76px; height: 37px; text-align: center;"><span style="font-weight: 400;">C30010020</span></td>
</tr>
<tr style="height: 37px;">
<td style="width: 286px; height: 37px;"><a href="https://www.diagenode.com/en/p/0-65-ml-bioruptor-microtubes-500-tubes">0.65 ml Pico Microtubes</a></td>
<td style="width: 76px; height: 37px; text-align: center;"><span style="font-weight: 400;">C30010011</span></td>
</tr>
<tr style="height: 37px;">
<td style="width: 286px; height: 37px;"><a href="https://www.diagenode.com/en/p/1-5-ml-bioruptor-microtubes-with-caps-300-tubes">1.5 ml Pico Microtubes</a></td>
<td style="width: 76px; height: 37px; text-align: center;"><span style="font-weight: 400;">C30010016</span></td>
</tr>
<tr style="height: 37px;">
<td style="width: 286px; height: 37px;"><a href="https://www.diagenode.com/en/p/15-ml-bioruptor-tubes-50-pc">15 ml Pico Tubes</a></td>
<td style="width: 76px; height: 37px; text-align: center;"><span style="font-weight: 400;">C30010017</span></td>
</tr>
<tr style="height: 37px;">
<td style="width: 286px; height: 37px;"><a href="https://www.diagenode.com/en/p/15-ml-bioruptor-tubes-sonication-beads-50-rxns">15 ml Pico Tubes & sonication beads</a></td>
<td style="width: 76px; height: 37px; text-align: center;"><span style="font-weight: 400;">C01020031</span></td>
</tr>
</tbody>
</table>
<p><a href="https://www.diagenode.com/files/products/shearing_technology/bioruptor_accessories/TDS-BioruptorTubes.pdf">Find datasheet for Diagenode tubes here</a></p>
<p><a href="../documents/bioruptor-organigram-tubes">Which tubes for which Bioruptor®?</a></p>',
'label3' => 'Available shearing Kits',
'info3' => '<p>Diagenode has optimized a range of solutions for <strong>successful chromatin preparation</strong>. Chromatin EasyShear Kits together with the Pico ultrasonicator combine the benefits of efficient cell lysis and chromatin shearing, while keeping epitopes accessible to the antibody, critical for efficient chromatin immunoprecipitation. Each Chromatin EasyShear Kit provides optimized reagents and a thoroughly validated protocol according to your specific experimental needs. SDS concentration is adapted to each workflow taking into account target-specific requirements.</p>
<p>For best results, choose your desired ChIP kit followed by the corresponding Chromatin EasyShear Kit (to optimize chromatin shearing ). The Chromatin EasyShear Kits can be used independently of Diagenode’s ChIP kits for chromatin preparation prior to any chromatin immunoprecipitation protocol. Choose an appropriate kit for your specific experimental needs.</p>
<h2>Kit choice guide</h2>
<table style="border: 0;" valign="center">
<tbody>
<tr style="background: #fff;">
<th class="text-center"></th>
<th class="text-center" style="font-size: 17px;">SAMPLE TYPE</th>
<th class="text-center" style="font-size: 17px;">SAMPLE INPUT</th>
<th class="text-center" style="font-size: 17px;">KIT</th>
<th class="text-center" style="font-size: 17px;">SDS<br /> CONCENTRATION</th>
<th class="text-center" style="font-size: 17px;">NUCLEI<br /> ISOLATION</th>
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<tr style="background: #fff;">
<td colspan="7"></td>
</tr>
<tr style="background: #fff;">
<td rowspan="5"><img src="https://www.diagenode.com/img/label-histones.png" /></td>
<td class="text-center" style="border-bottom: 1px solid #dedede;">
<div class="label alert" style="font-size: 17px;">CELLS</div>
</td>
<td class="text-center" style="font-size: 17px; border-bottom: 1px solid #dedede;">< 100,000</td>
<td class="text-center" style="font-size: 17px; border-bottom: 1px solid #dedede;"><a href="https://www.diagenode.com/en/p/chromatin-shearing-optimization-kit-high-sds-100-million-cells">Chromatin EasyShear Kit<br />High SDS</a></td>
<td class="text-center" style="font-size: 17px; border-bottom: 1px solid #dedede;">1%</td>
<td class="text-center" style="border-bottom: 1px solid #dedede;"><img src="https://www.diagenode.com/img/cross-unvalid-green.jpg" width="18" height="20" /></td>
</tr>
<tr style="background: #fff; border-bottom: 1px solid #dedede;">
<td class="text-center">
<div class="label alert" style="font-size: 17px;">CELLS</div>
</td>
<td class="text-center" style="font-size: 17px;">> 100,000</td>
<td class="text-center" style="font-size: 17px;"><a href="https://www.diagenode.com/en/p/chromatin-easyshear-kit-ultra-low-sds">Chromatin EasyShear Kit<br />Ultra Low SDS</a></td>
<td class="text-center" style="font-size: 17px;">< 0.1%</td>
<td class="text-center"><img src="https://www.diagenode.com/img/valid.png" width="20" height="16" /></td>
</tr>
<tr style="background: #fff; border-bottom: 1px solid #dedede;">
<td class="text-center">
<div class="label alert" style="font-size: 17px;">TISSUE</div>
</td>
<td class="text-center"></td>
<td class="text-center" style="font-size: 17px;"><a href="https://www.diagenode.com/en/p/chromatin-easyshear-kit-ultra-low-sds">Chromatin EasyShear Kit<br />Ultra Low SDS</a></td>
<td class="text-center" style="font-size: 17px;">< 0.1%</td>
<td class="text-center"><img src="https://www.diagenode.com/img/valid.png" width="20" height="16" /></td>
</tr>
<tr style="background: #fff; border-bottom: 1px solid #dedede;">
<td class="text-center">
<div class="label alert" style="font-size: 17px;">PLANT TISSUE</div>
</td>
<td class="text-center"></td>
<td class="text-center" style="font-size: 17px;"><a href="https://www.diagenode.com/en/p/chromatin-shearing-plant-chip-seq-kit">Chromatin EasyShear Kit<br />for Plant</a></td>
<td class="text-center" style="font-size: 17px;">0.5%</td>
<td class="text-center"><img src="https://www.diagenode.com/img/valid.png" width="20" height="16" /></td>
</tr>
<tr style="background: #fff;">
<td class="text-center">
<div class="label alert" style="font-size: 17px;">FFPE SAMPLES</div>
</td>
<td class="text-center"></td>
<td class="text-center" style="font-size: 17px;"><a href="https://www.diagenode.com/en/p/chromatin-easyshear-kit-low-sds">Chromatin EasyShear Kit<br />Low SDS</a></td>
<td class="text-center" style="font-size: 17px;">0.2%</td>
<td class="text-center"><img src="https://www.diagenode.com/img/valid.png" width="20" height="16" /></td>
</tr>
<tr style="background: #fff;">
<td colspan="7"></td>
</tr>
<tr style="background: #fff;">
<td rowspan="6"><img src="https://www.diagenode.com/img/label-tf.png" /></td>
<td colspan="6"></td>
</tr>
<tr style="background: #fff;">
<td colspan="6"></td>
</tr>
<tr style="background: #fff;">
<td class="text-center">
<div class="label alert" style="font-size: 17px;">CELLS</div>
</td>
<td class="text-center"></td>
<td rowspan="3" class="text-center" style="font-size: 17px;"><a href="https://www.diagenode.com/en/p/chromatin-easyshear-kit-low-sds">Chromatin EasyShear Kit<br />Low SDS</a></td>
<td rowspan="3" class="text-center" style="font-size: 17px;">0.2%</td>
<td rowspan="3" class="text-center"><img src="https://www.diagenode.com/img/valid.png" width="20" height="16" /></td>
</tr>
<tr style="background: #fff;">
<td class="text-center">
<div class="label alert" style="font-size: 17px;">TISSUE</div>
</td>
<td class="text-center"></td>
</tr>
<tr style="background: #fff;">
<td class="text-center">
<div class="label alert" style="font-size: 17px;">FFPE SAMPLES</div>
</td>
<td class="text-center"></td>
</tr>
<tr style="background: #fff;">
<td colspan="6"></td>
</tr>
</tbody>
</table>
<div class="extra-spaced">
<h3>Guide for optimal chromatin preparation using Chromatin EasyShear Kits <i class="fa fa-arrow-circle-right"></i> <a href="https://www.diagenode.com/pages/chromatin-prep-easyshear-kit-guide">Read more</a></h3>
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'description' => '<p><span>The tube holder for 1.5 ml tubes has been especially designed for being used with the <strong>Bioruptor® Pico</strong> and to guarantee homogeneity of chromatin or DNA shearing. It allows for reproducible sonication of up to<strong> 6 x 1.5 ml tubes</strong> at a time with a <strong>sample volume range of 100 to 300 µl</strong>. The holder is made up of a tube holder and its specific dock that makes the sample preparation more ergonomic. <br /></span></p>',
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<div class="small-12 medium-12 large-12 columns">In recent years, advances in Next-Generation Sequencing (NGS) have revolutionized genomics and biology. This growth has fueled demands on upstream techniques for optimal sample preparation and genomic library construction. One of the most critical aspects of optimal library preparation is the quality of the DNA to be sequenced. The DNA must first be effectively and consistently sheared into the appropriate fragment size (depending on the sequencing platform) to enable sensitive and reliable NGS results. The <strong>Bioruptor</strong><sup>®</sup> <strong>Pico</strong> and the <strong>Megaruptor</strong><sup>®</sup> provide superior sample yields, fragment size, and consistency, which are essential for Next-Generation Sequencing workflows. Follow our guidelines and find the good parameters for your expected DNA size: <a href="https://pybrevet.typeform.com/to/o8cQfM">DNA shearing with the Bioruptor<sup>®</sup></a>.</div>
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<p></p>
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<div class="small-7 medium-7 large-7 columns text-center"><img src="https://www.diagenode.com/img/applications/true-flexibility-with-br-ngs.jpg" /></div>
<div class="small-5 medium-5 large-5 columns"><small><strong>Programmable DNA size distribution and high reproducibility with Bioruptor<sup>®</sup> Pico using 0.65 (panel A) or 0.1 ml (panel B) microtubes</strong>. <b>Panel A:</b> 200 bp after 13 cycles (13 sec ON/OFF) using 100 µl volume. Average size: 204; CV%:1.89%). <b>Panel B:</b> 200 bp after 20 cycles (30 sec ON/OFF) using 10 µl volume. (Average size: 215 bp; CV%: 6.6%). <b>Panel A & B:</b> peak electropherogram view. <b>Panel C & D:</b> virtual gel view.</small></div>
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<p><br /><br /></p>
<div class="row">
<div class="small-10 medium-10 large-10 columns text-center end small-offset-1"><img src="https://www.diagenode.com/img/applications/megaruptor-short-frag.jpg" /></div>
<div class="small-12 medium-12 large-12 columns"><small><strong> Reproducible and narrow DNA size distribution with Megaruptor® using short fragment size Hydropores Validation using two different DNA sources and two different methods of analysis. A:</strong> Shearing of lambda phage genomic DNA (20 ng/μl; 150 μl/sample) sheared at different speed settings and analyzed on 1% agarose gel. <strong>B:</strong> Bioanalyzer profiles of human genomic DNA (20 ng/μl; 150 μl/sample) sheared at different software settings of 2 and 5 kb. Three independent experiments were run for each setting. (Agilent DNA 12000 kit was used for separation and fragment sizing).</small></div>
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<p><br /><br /></p>
<div class="row">
<div class="small-4 medium-4 large-4 columns text-center"><img src="https://www.diagenode.com/img/applications/megaruptor-long-frag.jpg" /></div>
<div class="small-8 medium-8 large-8 columns"><small><strong> Demonstrated shearing to fragment sizes between 15 kb and 75 kb with Megaruptor® using long fragment size Hydropores. </strong>Image shows DNA size distribution of human genomic DNA sheared with long fragment Hydropores. DNA was analyzed by pulsed field gel electrophoresis (PFGE) in 1% agarose gel and a mean size of smears was estimated using Image Lab 4.1 software.<br /> * indicates unsheared DNA </small></div>
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<div class="small-12 medium-12 large-12 columns">The most important steps for a successful ChIP include both cell fixation and lysis, and chromatin shearing. Researchers often overlook the critical nature of both of these steps. Eliminating inconsistencies in the shearing step, <strong>Diagenode's Bioruptor</strong><sup>®</sup> uses state-of-the-art ultrasound <strong>ACT</strong> (<strong>A</strong>daptive <strong>C</strong>avitation <strong>T</strong>echnology) to efficiently shear chromatin. ACT enables the highest chromatin quality for high IP efficiency and sensitivity for ChIP experiments with gentle yet highly effective shearing forces. Additionally, the Bioruptor<sup>®</sup> provides a precisely controlled temperature environment that preserves chromatin from heat degradation such that protein-DNA complexes are well-preserved for sensitive, unbiased, and accurate ChIP.<br /><br /> <strong>Diagenode's Bioruptor</strong><sup>®</sup> is the instrument of choice for chromatin shearing used for a number of downstream applications such as qPCR and ChIP-seq that require optimally sheared, unbiased chromatin.</div>
<div class="small-12 medium-12 large-12 columns text-center"><br /><img src="https://www.diagenode.com/img/applications/pico_dna_shearing_fig2.png" /></div>
<div class="small-10 medium-10 large-10 columns end small-offset-1"><small> <br /><strong>Panel A, 10 µl volume:</strong> Chromatin samples are sheared for 10, 20 and 30 cycles of 30 sec ON/30 sec OFF with the Bioruptor® Pico using 0.1 ml Bioruptor® Microtubes (Cat. No. B01200041). <strong>Panel B, 100 µl volume:</strong> Chromatin samples are sheared for 10 cycles of 30 sec ON/30 sec OFF with the Bioruptor® Pico using 0.65 ml Bioruptor® Microtubes (Cat. No. WA-005-0500). <strong>Panel C, 300 µl volume:</strong> Chromatin samples are sheared for 5, 10 and 15 cycles of 30 sec ON/30 sec OFF with the Bioruptor® Pico using using 1.5 ml Bioruptor microtubes (Cat. No. C30010016). Prior to de-crosslinking, samples are treated with RNase cocktail mixture at 37°C during 1 hour. The sheared chromatin is then de-crosslinked overnight and phenol/chloroform purified as described in the kit manual. 10 µl of DNA (equivalent of 500, 000 cells) are analyzed on a 2% agarose gel (MW corresponds to the 100 bp DNA molecular weight marker).</small></div>
<div class="small-12 medium-12 large-12 columns"><br /><br /></div>
<div class="small-12 medium-12 large-12 columns">
<p>It is important to establish optimal conditions to shear crosslinked chromatin to get the correct fragment sizes needed for ChIP. Usually this process requires both optimizing sonication conditions as well as optimizing SDS concentration, which is laborious. With the Chromatin Shearing Optimization Kits, optimization is fast and easy - we provide optimization reagents with varying concentrations of SDS. Moreover, our Chromatin Shearing Optimization Kits can be used for the optimization of chromatin preparation with our kits for ChIP.</p>
</div>
<div class="small-12 medium-12 large-12 columns">
<div class="page" title="Page 7">
<table>
<tbody>
<tr valign="middle">
<td></td>
<td style="text-align: center;"><strong><a href="https://www.diagenode.com/p/chromatin-shearing-optimization-kit-low-sds-100-million-cells">Chromatin Shearing Kit Low SDS (for Histone)</a></strong></td>
<td style="text-align: center;"><strong><a href="https://www.diagenode.com/p/chromatin-shearing-optimization-kit-low-sds-for-tfs-25-rxns">Chromatin Shearing Kit Low SDS (for TF)</a></strong></td>
<td style="text-align: center;"><strong><a href="https://www.diagenode.com/p/chromatin-shearing-optimization-kit-high-sds-100-million-cells">Chromatin Shearing Kit High SDS</a></strong></td>
<td style="text-align: center;"><strong><a href="https://www.diagenode.com/p/chromatin-shearing-optimization-kit-medium-sds-100-million-cells">Chromatin Shearing Kit (for Plant)</a></strong></td>
</tr>
<tr valign="middle" style="background-color: #fff;">
<td>
<p><strong>SDS concentration</strong></p>
</td>
<td style="text-align: center;">
<p>< 0.1%</p>
</td>
<td style="text-align: center;">
<p>0.2%</p>
</td>
<td style="text-align: center;">
<p>1%</p>
</td>
<td style="text-align: center;">
<p>0.5%</p>
</td>
</tr>
<tr valign="middle" style="background-color: #fff;">
<td>
<p><strong>Nuclei isolation</strong></p>
</td>
<td style="text-align: center;">
<p>Yes</p>
</td>
<td style="text-align: center;">
<p>Yes</p>
</td>
<td style="text-align: center;">
<p>No</p>
</td>
<td style="text-align: center;">
<p>Yes</p>
</td>
</tr>
<tr valign="middle" style="background-color: #fff;">
<td>
<p><strong>Allows for shearing of... cells/tissue</strong></p>
</td>
<td style="text-align: center;">
<p>100 million cells</p>
</td>
<td style="text-align: center;">
<p>100 million cells</p>
</td>
<td style="text-align: center;">
<p>100 million cells</p>
</td>
<td style="text-align: center;">
<p>up to 25 g of tissue</p>
</td>
</tr>
<tr valign="middle" style="background-color: #fff;">
<td>
<p><strong>Corresponding to shearing buffers from</strong></p>
</td>
<td style="text-align: center;">
<p><a href="https://www.diagenode.com/en/p/ideal-chip-seq-kit-x24-24-rxns">iDeal ChIP-seq kit for Histones</a></p>
</td>
<td style="text-align: center;">
<p><a href="https://www.diagenode.com/en/p/ideal-chip-seq-kit-for-transcription-factors-x24-24-rxns">iDeal ChIP-seq Kit for Transcription Factors</a></p>
<p><a href="https://www.diagenode.com/en/p/ideal-chip-qpcr-kit">iDeal ChIP qPCR kit</a></p>
</td>
<td style="text-align: center;">
<p><a href="https://www.diagenode.com/en/p/true-microchip-kit-x16-16-rxns">True MicroChIP kit</a></p>
</td>
<td style="text-align: center;">
<p><a href="https://www.diagenode.com/en/p/universal-plant-chip-seq-kit-x24-24-rxns">Universal Plant ChIP-seq kit</a></p>
</td>
</tr>
</tbody>
</table>
<p><em><span style="font-weight: 400;">Table comes from our </span><a href="https://www.diagenode.com/protocols/bioruptor-pico-chromatin-preparation-guide"><span style="font-weight: 400;">Guide for successful chromatin preparation using the Bioruptor® Pico</span></a></em></p>
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<p><span>The 1.5 ml Bioruptor</span><span>® </span><span>Microtubes </span><strong>C30010016 </strong><span>for chromatin shearing strongly improve chromatin sonication efficiency. These tubes have been thoroughly validated for use on the Bioruptor</span><span>® </span><span>Pico (B01060001) and are strongly recommended for DNA and chromatin shearing applications using this instrument. </span></p>
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'description' => '<p><span>Therapeutic targeting of the estrogen receptor (ER) is a clinically validated approach for estrogen receptor positive breast cancer (ER+ BC), but sustained response is limited by acquired resistance. Targeting the transcriptional coactivators required for estrogen receptor activity represents an alternative approach that is not subject to the same limitations as targeting estrogen receptor itself. In this report we demonstrate that the acetyltransferase activity of coactivator paralogs CREBBP/EP300 represents a promising therapeutic target in ER+ BC. Using the potent and selective inhibitor CPI-1612, we show that CREBBP/EP300 acetyltransferase inhibition potently suppresses in vitro and in vivo growth of breast cancer cell line models and acts in a manner orthogonal to directly targeting ER. CREBBP/EP300 acetyltransferase inhibition suppresses ER-dependent transcription by targeting lineage-specific enhancers defined by the pioneer transcription factor FOXA1. These results validate CREBBP/EP300 acetyltransferase activity as a viable target for clinical development in ER+ breast cancer.</span></p>',
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'description' => '<p>Mutually exclusive expression of the var multigene family is key to immune evasion and pathogenesis in Plasmodium falciparum, but few factors have been shown to play a direct role. We adapted a CRISPR-based proteomics approach to identify novel factors associated with var genes in their natural chromatin context. Catalytically inactive Cas9 ("dCas9") was targeted to var gene regulatory elements, immunoprecipitated, and analyzed with mass spectrometry. Known and novel factors were enriched including structural proteins, DNA helicases, and chromatin remodelers. Functional characterization of PfISWI, an evolutionarily divergent putative chromatin remodeler enriched at the var gene promoter, revealed a role in transcriptional activation. Proteomics of PfISWI identified several proteins enriched at the var gene promoter such as acetyl-CoA synthetase, a putative MORC protein, and an ApiAP2 transcription factor. These findings validate the CRISPR/dCas9 proteomics method and define a new var gene-associated chromatin complex. This study establishes a tool for targeted chromatin purification of unaltered genomic loci and identifies novel chromatin-associated factors potentially involved in transcriptional control and/or chromatin organization of virulence genes in the human malaria parasite.</p>',
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'description' => '<p>A surprising complexity of ubiquitin signaling has emerged with identification of different ubiquitin chain topologies. However, mechanisms of how the diverse ubiquitin codes control biological processes remain poorly understood. Here, we use quantitative whole-proteome mass spectrometry to identify yeast proteins that are regulated by lysine 11 (K11)-linked ubiquitin chains. The entire Met4 pathway, which links cell proliferation with sulfur amino acid metabolism, was significantly affected by K11 chains and selected for mechanistic studies. Previously, we demonstrated that a K48-linked ubiquitin chain represses the transcription factor Met4. Here, we show that efficient Met4 activation requires a K11-linked topology. Mechanistically, our results propose that the K48 chain binds to a topology-selective tandem ubiquitin binding region in Met4 and competes with binding of the basal transcription machinery to the same region. The change to K11-enriched chain architecture releases this competition and permits binding of the basal transcription complex to activate transcription.</p>',
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'pmid' => 'http://www.pubmed.gov/31444107',
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'description' => '<p>Wilms tumors are the most common type of pediatric kidney tumors. While the overall prognosis for patients is favorable, especially tumors that exhibit a blastemal subtype after preoperative chemotherapy have a poor prognosis. For an improved risk assessment and therapy stratification, it is essential to identify the driving factors that are distinctive for this aggressive subtype. In our study, we compared gene expression profiles of 33 tumor biopsies (17 blastemal and 16 other tumors) after neoadjuvant chemotherapy. The analysis of this dataset using the Regulator Gene Association Enrichment algorithm successfully identified several biomarkers and associated molecular mechanisms that distinguish between blastemal and nonblastemal Wilms tumors. Specifically, regulators involved in embryonic development and epigenetic processes like chromatin remodeling and histone modification play an essential role in blastemal tumors. In this context, we especially identified TCF3 as the central regulatory element. Furthermore, the comparison of ChIP-Seq data of Wilms tumor cell cultures from a blastemal mouse xenograft and a stromal tumor provided further evidence that the chromatin states of blastemal cells share characteristics with embryonic stem cells that are not present in the stromal tumor cell line. These stem-cell like characteristics could potentially add to the increased malignancy and chemoresistance of the blastemal subtype. Along with TCF3, we detected several additional biomarkers that are distinctive for blastemal Wilms tumors after neoadjuvant chemotherapy and that may provide leads for new therapeutic regimens.</p>',
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'pmid' => 'http://www.pubmed.gov/30155889',
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'authors' => 'Sebastian Baumgarten, Jessica M. Bryant, Ameya Sinha, Thibaud Reyser, Peter R. Preiser, Peter C. Dedon, Artur Scherf',
'description' => '<p>Malaria pathogenesis results from the asexual replication of Plasmodium falciparum within human red blood cells, which relies on a precisely timed cascade of gene expression over a 48-hour life cycle. Although substantial post-transcriptional regulation of this hardwired program has been observed, it remains unclear how these processes are mediated on a transcriptome-wide level. To this end, we identified mRNA modifications in the P. falciparum transcriptome and performed a comprehensive characterization of N6-methyladenosine (m6A) over the course of blood stage development. Using mass spectrometry and m6A RNA sequencing, we demonstrate that m6A is highly developmentally regulated, exceeding m6A levels known in any other eukaryote. We identify an evolutionarily conserved m6A writer complex and show that knockdown of the putative m6A methyltransferase by CRISPR interference leads to increased levels of transcripts that normally contain m6A. In accordance, we find an inverse correlation between m6A status and mRNA stability or translational efficiency. Our data reveal the crucial role of extensive m6A mRNA methylation in dynamically fine-tuning the transcriptional program of a unicellular eukaryote as well as a new ‘epitranscriptomic’ layer of gene regulation in malaria parasites.</p>',
'date' => '2019-03-09',
'pmid' => 'https://www.nature.com/articles/s41564-019-0521-7',
'doi' => '10.1101/572891.',
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'name' => 'Dot1 promotes H2B ubiquitination by a methyltransferase-independent mechanism.',
'authors' => 'van Welsem T, Korthout T, Ekkebus R, Morais D, Molenaar TM, van Harten K, Poramba-Liyanage DW, Sun SM, Lenstra TL, Srivas R, Ideker T, Holstege FCP, van Attikum H, El Oualid F, Ovaa H, Stulemeijer IJE, Vlaming H, van Leeuwen F',
'description' => '<p>The histone methyltransferase Dot1 is conserved from yeast to human and methylates lysine 79 of histone H3 (H3K79) on the core of the nucleosome. H3K79 methylation by Dot1 affects gene expression and the response to DNA damage, and is enhanced by monoubiquitination of the C-terminus of histone H2B (H2Bub1). To gain more insight into the functions of Dot1, we generated genetic interaction maps of increased-dosage alleles of DOT1. We identified a functional relationship between increased Dot1 dosage and loss of the DUB module of the SAGA co-activator complex, which deubiquitinates H2Bub1 and thereby negatively regulates H3K79 methylation. Increased Dot1 dosage was found to promote H2Bub1 in a dose-dependent manner and this was exacerbated by the loss of SAGA-DUB activity, which also caused a negative genetic interaction. The stimulatory effect on H2B ubiquitination was mediated by the N-terminus of Dot1, independent of methyltransferase activity. Our findings show that Dot1 and H2Bub1 are subject to bi-directional crosstalk and that Dot1 possesses chromatin regulatory functions that are independent of its methyltransferase activity.</p>',
'date' => '2018-09-08',
'pmid' => 'http://www.pubmed.gov/30203048',
'doi' => '10.1093/nar/gky801',
'modified' => '2018-11-09 12:13:19',
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'name' => 'BET protein inhibition sensitizes glioblastoma cells to temozolomidetreatment by attenuating MGMT expression',
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'description' => '<p>Bromodomain and extra-terminal tail (BET) proteins have been identified as potential epigenetic targets in cancer, including glioblastoma. These epigenetic modifiers link the histone code to gene transcription that can be disrupted with small molecule BET inhibitors (BETi). With the aim of developing rational combination treatments for glioblastoma, we analyzed BETi-induced differential gene expression in glioblastoma derived-spheres, and identified 6 distinct response patterns. To uncover emerging actionable vulnerabilities that can be targeted with a second drug, we extracted the 169 significantly disturbed DNA Damage Response genes and inspected their response pattern. The most prominent candidate with consistent downregulation, was the O-6-methylguanine-DNA methyltransferase (MGMT) gene, a known resistance factor for alkylating agent therapy in glioblastoma. BETi not only reduced MGMT expression in GBM cells, but also inhibited its induction, typically observed upon temozolomide treatment. To determine the potential clinical relevance, we evaluated the specificity of the effect on MGMT expression and MGMT mediated treatment resistance to temozolomide. BETi-mediated attenuation of MGMT expression was associated with reduction of BRD4- and Pol II-binding at the MGMT promoter. On the functional level, we demonstrated that ectopic expression of MGMT under an unrelated promoter was not affected by BETi, while under the same conditions, pharmacologic inhibition of MGMT restored the sensitivity to temozolomide, reflected in an increased level of g-H2AX, a proxy for DNA double-strand breaks. Importantly, expression of MSH6 and MSH2, which are required for sensitivity to unrepaired O6-methylGuanin-lesions, was only briefly affected by BETi. Taken together, the addition of BET-inhibitors to the current standard of care, comprising temozolomide treatment, may sensitize the 50\% of patients whose glioblastoma exert an unmethylated MGMT promoter.</p>',
'date' => '0000-00-00',
'pmid' => 'https://www.researchsquare.com/article/rs-1832996/v1',
'doi' => '10.21203/rs.3.rs-1832996/v1',
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<div class="small-12 columns" >
<h6 style="height:60px">Picoruptor 2 sonication device </h6>
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<a href="/jp/p/1-5-ml-tube-holder-dock-for-bioruptor-pico"><img src="/img/product/shearing_technologies/tube-holder-pico-2.jpg" alt="Bioruptor Pico Tube Holder" class="th"/></a> </div>
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<h6 style="height:60px">Tube holder for 1.5 ml tubes - Picoruptor</h6>
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<p><span>The Bioruptor® Pico is the latest innovation in shearing and represents a new breakthrough as an all-in-one shearing system capable of shearing samples from 150 bp to 1 kb. </span>Since 2004, Diagenode has accumulated <strong>shearing expertise</strong> to design the Bioruptor® Pico and guarantee the best experience with the <strong>sample preparation</strong> for <strong>number of applications -- in various fields of studies</strong> including environmental research, toxicology, genomics and epigenomics, cancer research, stem cells and development, neuroscience, clinical applications, agriculture, and many more.</p>
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<p>The Bioruptor Pico shearing accessories and consumables have been developed to allow <strong>flexibility in sample volumes</strong> (20 µl - 2 ml) and a <strong>fast parallel processing of samples</strong> (up to 16 samples simultaneously). <span>The built-in cooling system (Bioruptor® Cooler) ensures high precision <strong>temperature control</strong>. The <strong>user-friendly interface</strong> has been designed for any researcher, providing an easy and advanced modes that give both beginners and experienced users the right level of control. </span></p>
<p>In addition, Diagenode provides fully-validated tubes that remain <strong>budget-friendly with low operating cost</strong> (< 1€/$/DNA sample) and shearing kits for best sample quality. <span></span></p>
<p><strong>Application versatility</strong>:</p>
<ul>
<li>DNA shearing for Next-Generation-Sequencing</li>
<li>Chromatin shearing</li>
<li>RNA shearing</li>
<li>Protein extraction from tissues and cells (also for mass spectrometry)</li>
<li>FFPE DNA extraction</li>
<li>Protein aggregation studies</li>
<li>CUT&RUN - shearing of input DNA for NGS</li>
</ul>
<div style="background-color: #f1f3f4; margin: 10px; padding: 50px;">
<p><strong>Bioruptor Pico: Recommended for CUT&RUN sequencing for input DNA</strong><br /><br /> By combining antibody-targeted controlled cleavage by MNase and NGS, <strong>CUT&RUN sequencing</strong> can be used to identify protein-DNA binding sites genome-wide. CUT&RUN works by using the DNA cleaving activity of a Protein A-fused MNase to isolate DNA that is bound by a protein of interest. This targeted digestion is controlled by the addition of calcium, which MNase requires for its nuclease activity. After MNase digestion, short DNA fragments are released and can then be purified for subsequent library preparation and high-throughput sequencing. While CUT&RUN does not require mechanical shearing chromatin given the enzymatic approach, sonication is highly recommended for the fragmentation of the input DNA (used to compare the enriched sample) in order to be compatible with downstream NGS. The Bioruptor Pico is the ideal instrument of choice for generating optimal DNA fragments with a tight distribution, assuring excellent library prep and excellent sequencing results for your CUT&RUN assay.<br /><br /> <strong>Explore the Bioruptor Pico now.</strong></p>
</div>
<div class="extra-spaced"><img alt="Bioruptor Sonication for DNA shearing for Next-Generation-Sequencing" src="https://www.diagenode.com/img/product/shearing_technologies/guarantie.png" /></div>
<div class="extra-spaced"><center><img alt="Bioruptor Sonication for Chromatin shearing" src="https://www.diagenode.com/img/product/shearing_technologies/pico-reproducibility-is-priority.jpg" /></center></div>
<div class="extra-spaced"><center><a href="https://www.diagenode.com/en/pages/form-demo"> <img alt="Bioruptor Sonication for RNA shearing" src="https://www.diagenode.com/img/product/shearing_technologies/pico-request-demo.jpg" /></a></center></div>
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'label2' => 'View accessories & consumables for Bioruptor<sup>®</sup> Pico',
'info2' => '<h3>Shearing Accessories</h3>
<table style="width: 641px;">
<thead>
<tr style="background-color: #dddddd; height: 37px;">
<td style="width: 300px; height: 37px;"><strong>Name</strong></td>
<td style="width: 171px; text-align: center; height: 37px;">Catalog number</td>
<td style="width: 160px; text-align: center; height: 37px;">Throughput</td>
</tr>
</thead>
<tbody>
<tr style="height: 38px;">
<td style="width: 300px; height: 38px;"><a href="https://www.diagenode.com/en/p/0-2-ml-tube-holder-dock-for-bioruptor-pico">Tube holder for 0.2 ml tubes</a></td>
<td style="width: 171px; text-align: center; height: 38px;"><span style="font-weight: 400;">B01201144</span></td>
<td style="width: 160px; text-align: center; height: 38px;"><span style="font-weight: 400;">16 samples</span></td>
</tr>
<tr style="height: 38px;">
<td style="width: 300px; height: 38px;"><a href="https://www.diagenode.com/en/p/0-65-ml-tube-holder-dock-for-bioruptor-pico">Tube holder for 0.65 ml tubes</a></td>
<td style="width: 171px; text-align: center; height: 38px;"><span style="font-weight: 400;">B01201143</span></td>
<td style="width: 160px; text-align: center; height: 38px;"><span style="font-weight: 400;">12 samples<br /></span></td>
</tr>
<tr style="height: 38px;">
<td style="width: 300px; height: 38px;"><a href="https://www.diagenode.com/en/p/1-5-ml-tube-holder-dock-for-bioruptor-pico">Tube holder for 1.5 ml tubes</a></td>
<td style="width: 171px; text-align: center; height: 38px;"><span style="font-weight: 400;">B01201140</span></td>
<td style="width: 160px; text-align: center; height: 38px;"><span style="font-weight: 400;">6 samples<br /></span></td>
</tr>
<tr style="height: 37px;">
<td style="width: 300px; height: 37px;"><a href="https://www.diagenode.com/en/p/15-ml-sonication-accessories-for-bioruptor-standard-plus-pico-1-pack">15 ml sonication accessories</a></td>
<td style="width: 171px; text-align: center; height: 37px;"><span style="font-weight: 400;">B01200016</span></td>
<td style="width: 160px; text-align: center; height: 37px;"><span style="font-weight: 400;">6 samples<br /></span></td>
</tr>
</tbody>
</table>
<h3>Shearing Consumables</h3>
<table style="width: 646px;">
<thead>
<tr style="background-color: #dddddd; height: 37px;">
<td style="width: 286px; height: 37px;"><strong>Name</strong></td>
<td style="width: 76px; height: 37px; text-align: center;">Catalog Number</td>
</tr>
</thead>
<tbody>
<tr style="height: 37px;">
<td style="width: 286px; height: 37px;"><a href="https://www.diagenode.com/en/p/02ml-microtubes-for-bioruptor-pico">0.2 ml Pico Microtubes</a></td>
<td style="width: 76px; height: 37px; text-align: center;"><span style="font-weight: 400;">C30010020</span></td>
</tr>
<tr style="height: 37px;">
<td style="width: 286px; height: 37px;"><a href="https://www.diagenode.com/en/p/0-65-ml-bioruptor-microtubes-500-tubes">0.65 ml Pico Microtubes</a></td>
<td style="width: 76px; height: 37px; text-align: center;"><span style="font-weight: 400;">C30010011</span></td>
</tr>
<tr style="height: 37px;">
<td style="width: 286px; height: 37px;"><a href="https://www.diagenode.com/en/p/1-5-ml-bioruptor-microtubes-with-caps-300-tubes">1.5 ml Pico Microtubes</a></td>
<td style="width: 76px; height: 37px; text-align: center;"><span style="font-weight: 400;">C30010016</span></td>
</tr>
<tr style="height: 37px;">
<td style="width: 286px; height: 37px;"><a href="https://www.diagenode.com/en/p/15-ml-bioruptor-tubes-50-pc">15 ml Pico Tubes</a></td>
<td style="width: 76px; height: 37px; text-align: center;"><span style="font-weight: 400;">C30010017</span></td>
</tr>
<tr style="height: 37px;">
<td style="width: 286px; height: 37px;"><a href="https://www.diagenode.com/en/p/15-ml-bioruptor-tubes-sonication-beads-50-rxns">15 ml Pico Tubes & sonication beads</a></td>
<td style="width: 76px; height: 37px; text-align: center;"><span style="font-weight: 400;">C01020031</span></td>
</tr>
</tbody>
</table>
<p><a href="https://www.diagenode.com/files/products/shearing_technology/bioruptor_accessories/TDS-BioruptorTubes.pdf">Find datasheet for Diagenode tubes here</a></p>
<p><a href="../documents/bioruptor-organigram-tubes">Which tubes for which Bioruptor®?</a></p>',
'label3' => 'Available shearing Kits',
'info3' => '<p>Diagenode has optimized a range of solutions for <strong>successful chromatin preparation</strong>. Chromatin EasyShear Kits together with the Pico ultrasonicator combine the benefits of efficient cell lysis and chromatin shearing, while keeping epitopes accessible to the antibody, critical for efficient chromatin immunoprecipitation. Each Chromatin EasyShear Kit provides optimized reagents and a thoroughly validated protocol according to your specific experimental needs. SDS concentration is adapted to each workflow taking into account target-specific requirements.</p>
<p>For best results, choose your desired ChIP kit followed by the corresponding Chromatin EasyShear Kit (to optimize chromatin shearing ). The Chromatin EasyShear Kits can be used independently of Diagenode’s ChIP kits for chromatin preparation prior to any chromatin immunoprecipitation protocol. Choose an appropriate kit for your specific experimental needs.</p>
<h2>Kit choice guide</h2>
<table style="border: 0;" valign="center">
<tbody>
<tr style="background: #fff;">
<th class="text-center"></th>
<th class="text-center" style="font-size: 17px;">SAMPLE TYPE</th>
<th class="text-center" style="font-size: 17px;">SAMPLE INPUT</th>
<th class="text-center" style="font-size: 17px;">KIT</th>
<th class="text-center" style="font-size: 17px;">SDS<br /> CONCENTRATION</th>
<th class="text-center" style="font-size: 17px;">NUCLEI<br /> ISOLATION</th>
</tr>
<tr style="background: #fff;">
<td colspan="7"></td>
</tr>
<tr style="background: #fff;">
<td rowspan="5"><img src="https://www.diagenode.com/img/label-histones.png" /></td>
<td class="text-center" style="border-bottom: 1px solid #dedede;">
<div class="label alert" style="font-size: 17px;">CELLS</div>
</td>
<td class="text-center" style="font-size: 17px; border-bottom: 1px solid #dedede;">< 100,000</td>
<td class="text-center" style="font-size: 17px; border-bottom: 1px solid #dedede;"><a href="https://www.diagenode.com/en/p/chromatin-shearing-optimization-kit-high-sds-100-million-cells">Chromatin EasyShear Kit<br />High SDS</a></td>
<td class="text-center" style="font-size: 17px; border-bottom: 1px solid #dedede;">1%</td>
<td class="text-center" style="border-bottom: 1px solid #dedede;"><img src="https://www.diagenode.com/img/cross-unvalid-green.jpg" width="18" height="20" /></td>
</tr>
<tr style="background: #fff; border-bottom: 1px solid #dedede;">
<td class="text-center">
<div class="label alert" style="font-size: 17px;">CELLS</div>
</td>
<td class="text-center" style="font-size: 17px;">> 100,000</td>
<td class="text-center" style="font-size: 17px;"><a href="https://www.diagenode.com/en/p/chromatin-easyshear-kit-ultra-low-sds">Chromatin EasyShear Kit<br />Ultra Low SDS</a></td>
<td class="text-center" style="font-size: 17px;">< 0.1%</td>
<td class="text-center"><img src="https://www.diagenode.com/img/valid.png" width="20" height="16" /></td>
</tr>
<tr style="background: #fff; border-bottom: 1px solid #dedede;">
<td class="text-center">
<div class="label alert" style="font-size: 17px;">TISSUE</div>
</td>
<td class="text-center"></td>
<td class="text-center" style="font-size: 17px;"><a href="https://www.diagenode.com/en/p/chromatin-easyshear-kit-ultra-low-sds">Chromatin EasyShear Kit<br />Ultra Low SDS</a></td>
<td class="text-center" style="font-size: 17px;">< 0.1%</td>
<td class="text-center"><img src="https://www.diagenode.com/img/valid.png" width="20" height="16" /></td>
</tr>
<tr style="background: #fff; border-bottom: 1px solid #dedede;">
<td class="text-center">
<div class="label alert" style="font-size: 17px;">PLANT TISSUE</div>
</td>
<td class="text-center"></td>
<td class="text-center" style="font-size: 17px;"><a href="https://www.diagenode.com/en/p/chromatin-shearing-plant-chip-seq-kit">Chromatin EasyShear Kit<br />for Plant</a></td>
<td class="text-center" style="font-size: 17px;">0.5%</td>
<td class="text-center"><img src="https://www.diagenode.com/img/valid.png" width="20" height="16" /></td>
</tr>
<tr style="background: #fff;">
<td class="text-center">
<div class="label alert" style="font-size: 17px;">FFPE SAMPLES</div>
</td>
<td class="text-center"></td>
<td class="text-center" style="font-size: 17px;"><a href="https://www.diagenode.com/en/p/chromatin-easyshear-kit-low-sds">Chromatin EasyShear Kit<br />Low SDS</a></td>
<td class="text-center" style="font-size: 17px;">0.2%</td>
<td class="text-center"><img src="https://www.diagenode.com/img/valid.png" width="20" height="16" /></td>
</tr>
<tr style="background: #fff;">
<td colspan="7"></td>
</tr>
<tr style="background: #fff;">
<td rowspan="6"><img src="https://www.diagenode.com/img/label-tf.png" /></td>
<td colspan="6"></td>
</tr>
<tr style="background: #fff;">
<td colspan="6"></td>
</tr>
<tr style="background: #fff;">
<td class="text-center">
<div class="label alert" style="font-size: 17px;">CELLS</div>
</td>
<td class="text-center"></td>
<td rowspan="3" class="text-center" style="font-size: 17px;"><a href="https://www.diagenode.com/en/p/chromatin-easyshear-kit-low-sds">Chromatin EasyShear Kit<br />Low SDS</a></td>
<td rowspan="3" class="text-center" style="font-size: 17px;">0.2%</td>
<td rowspan="3" class="text-center"><img src="https://www.diagenode.com/img/valid.png" width="20" height="16" /></td>
</tr>
<tr style="background: #fff;">
<td class="text-center">
<div class="label alert" style="font-size: 17px;">TISSUE</div>
</td>
<td class="text-center"></td>
</tr>
<tr style="background: #fff;">
<td class="text-center">
<div class="label alert" style="font-size: 17px;">FFPE SAMPLES</div>
</td>
<td class="text-center"></td>
</tr>
<tr style="background: #fff;">
<td colspan="6"></td>
</tr>
</tbody>
</table>
<div class="extra-spaced">
<h3>Guide for optimal chromatin preparation using Chromatin EasyShear Kits <i class="fa fa-arrow-circle-right"></i> <a href="https://www.diagenode.com/pages/chromatin-prep-easyshear-kit-guide">Read more</a></h3>
</div>
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<div class="small-12 medium-12 large-12 columns">In recent years, advances in Next-Generation Sequencing (NGS) have revolutionized genomics and biology. This growth has fueled demands on upstream techniques for optimal sample preparation and genomic library construction. One of the most critical aspects of optimal library preparation is the quality of the DNA to be sequenced. The DNA must first be effectively and consistently sheared into the appropriate fragment size (depending on the sequencing platform) to enable sensitive and reliable NGS results. The <strong>Bioruptor</strong><sup>®</sup> <strong>Pico</strong> and the <strong>Megaruptor</strong><sup>®</sup> provide superior sample yields, fragment size, and consistency, which are essential for Next-Generation Sequencing workflows. Follow our guidelines and find the good parameters for your expected DNA size: <a href="https://pybrevet.typeform.com/to/o8cQfM">DNA shearing with the Bioruptor<sup>®</sup></a>.</div>
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<div class="small-7 medium-7 large-7 columns text-center"><img src="https://www.diagenode.com/img/applications/true-flexibility-with-br-ngs.jpg" /></div>
<div class="small-5 medium-5 large-5 columns"><small><strong>Programmable DNA size distribution and high reproducibility with Bioruptor<sup>®</sup> Pico using 0.65 (panel A) or 0.1 ml (panel B) microtubes</strong>. <b>Panel A:</b> 200 bp after 13 cycles (13 sec ON/OFF) using 100 µl volume. Average size: 204; CV%:1.89%). <b>Panel B:</b> 200 bp after 20 cycles (30 sec ON/OFF) using 10 µl volume. (Average size: 215 bp; CV%: 6.6%). <b>Panel A & B:</b> peak electropherogram view. <b>Panel C & D:</b> virtual gel view.</small></div>
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<div class="small-10 medium-10 large-10 columns text-center end small-offset-1"><img src="https://www.diagenode.com/img/applications/megaruptor-short-frag.jpg" /></div>
<div class="small-12 medium-12 large-12 columns"><small><strong> Reproducible and narrow DNA size distribution with Megaruptor® using short fragment size Hydropores Validation using two different DNA sources and two different methods of analysis. A:</strong> Shearing of lambda phage genomic DNA (20 ng/μl; 150 μl/sample) sheared at different speed settings and analyzed on 1% agarose gel. <strong>B:</strong> Bioanalyzer profiles of human genomic DNA (20 ng/μl; 150 μl/sample) sheared at different software settings of 2 and 5 kb. Three independent experiments were run for each setting. (Agilent DNA 12000 kit was used for separation and fragment sizing).</small></div>
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<div class="small-8 medium-8 large-8 columns"><small><strong> Demonstrated shearing to fragment sizes between 15 kb and 75 kb with Megaruptor® using long fragment size Hydropores. </strong>Image shows DNA size distribution of human genomic DNA sheared with long fragment Hydropores. DNA was analyzed by pulsed field gel electrophoresis (PFGE) in 1% agarose gel and a mean size of smears was estimated using Image Lab 4.1 software.<br /> * indicates unsheared DNA </small></div>
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<div class="small-12 medium-12 large-12 columns">The most important steps for a successful ChIP include both cell fixation and lysis, and chromatin shearing. Researchers often overlook the critical nature of both of these steps. Eliminating inconsistencies in the shearing step, <strong>Diagenode's Bioruptor</strong><sup>®</sup> uses state-of-the-art ultrasound <strong>ACT</strong> (<strong>A</strong>daptive <strong>C</strong>avitation <strong>T</strong>echnology) to efficiently shear chromatin. ACT enables the highest chromatin quality for high IP efficiency and sensitivity for ChIP experiments with gentle yet highly effective shearing forces. Additionally, the Bioruptor<sup>®</sup> provides a precisely controlled temperature environment that preserves chromatin from heat degradation such that protein-DNA complexes are well-preserved for sensitive, unbiased, and accurate ChIP.<br /><br /> <strong>Diagenode's Bioruptor</strong><sup>®</sup> is the instrument of choice for chromatin shearing used for a number of downstream applications such as qPCR and ChIP-seq that require optimally sheared, unbiased chromatin.</div>
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<div class="small-10 medium-10 large-10 columns end small-offset-1"><small> <br /><strong>Panel A, 10 µl volume:</strong> Chromatin samples are sheared for 10, 20 and 30 cycles of 30 sec ON/30 sec OFF with the Bioruptor® Pico using 0.1 ml Bioruptor® Microtubes (Cat. No. B01200041). <strong>Panel B, 100 µl volume:</strong> Chromatin samples are sheared for 10 cycles of 30 sec ON/30 sec OFF with the Bioruptor® Pico using 0.65 ml Bioruptor® Microtubes (Cat. No. WA-005-0500). <strong>Panel C, 300 µl volume:</strong> Chromatin samples are sheared for 5, 10 and 15 cycles of 30 sec ON/30 sec OFF with the Bioruptor® Pico using using 1.5 ml Bioruptor microtubes (Cat. No. C30010016). Prior to de-crosslinking, samples are treated with RNase cocktail mixture at 37°C during 1 hour. The sheared chromatin is then de-crosslinked overnight and phenol/chloroform purified as described in the kit manual. 10 µl of DNA (equivalent of 500, 000 cells) are analyzed on a 2% agarose gel (MW corresponds to the 100 bp DNA molecular weight marker).</small></div>
<div class="small-12 medium-12 large-12 columns"><br /><br /></div>
<div class="small-12 medium-12 large-12 columns">
<p>It is important to establish optimal conditions to shear crosslinked chromatin to get the correct fragment sizes needed for ChIP. Usually this process requires both optimizing sonication conditions as well as optimizing SDS concentration, which is laborious. With the Chromatin Shearing Optimization Kits, optimization is fast and easy - we provide optimization reagents with varying concentrations of SDS. Moreover, our Chromatin Shearing Optimization Kits can be used for the optimization of chromatin preparation with our kits for ChIP.</p>
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<div class="small-12 medium-12 large-12 columns">
<div class="page" title="Page 7">
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<tbody>
<tr valign="middle">
<td></td>
<td style="text-align: center;"><strong><a href="https://www.diagenode.com/p/chromatin-shearing-optimization-kit-low-sds-100-million-cells">Chromatin Shearing Kit Low SDS (for Histone)</a></strong></td>
<td style="text-align: center;"><strong><a href="https://www.diagenode.com/p/chromatin-shearing-optimization-kit-low-sds-for-tfs-25-rxns">Chromatin Shearing Kit Low SDS (for TF)</a></strong></td>
<td style="text-align: center;"><strong><a href="https://www.diagenode.com/p/chromatin-shearing-optimization-kit-high-sds-100-million-cells">Chromatin Shearing Kit High SDS</a></strong></td>
<td style="text-align: center;"><strong><a href="https://www.diagenode.com/p/chromatin-shearing-optimization-kit-medium-sds-100-million-cells">Chromatin Shearing Kit (for Plant)</a></strong></td>
</tr>
<tr valign="middle" style="background-color: #fff;">
<td>
<p><strong>SDS concentration</strong></p>
</td>
<td style="text-align: center;">
<p>< 0.1%</p>
</td>
<td style="text-align: center;">
<p>0.2%</p>
</td>
<td style="text-align: center;">
<p>1%</p>
</td>
<td style="text-align: center;">
<p>0.5%</p>
</td>
</tr>
<tr valign="middle" style="background-color: #fff;">
<td>
<p><strong>Nuclei isolation</strong></p>
</td>
<td style="text-align: center;">
<p>Yes</p>
</td>
<td style="text-align: center;">
<p>Yes</p>
</td>
<td style="text-align: center;">
<p>No</p>
</td>
<td style="text-align: center;">
<p>Yes</p>
</td>
</tr>
<tr valign="middle" style="background-color: #fff;">
<td>
<p><strong>Allows for shearing of... cells/tissue</strong></p>
</td>
<td style="text-align: center;">
<p>100 million cells</p>
</td>
<td style="text-align: center;">
<p>100 million cells</p>
</td>
<td style="text-align: center;">
<p>100 million cells</p>
</td>
<td style="text-align: center;">
<p>up to 25 g of tissue</p>
</td>
</tr>
<tr valign="middle" style="background-color: #fff;">
<td>
<p><strong>Corresponding to shearing buffers from</strong></p>
</td>
<td style="text-align: center;">
<p><a href="https://www.diagenode.com/en/p/ideal-chip-seq-kit-x24-24-rxns">iDeal ChIP-seq kit for Histones</a></p>
</td>
<td style="text-align: center;">
<p><a href="https://www.diagenode.com/en/p/ideal-chip-seq-kit-for-transcription-factors-x24-24-rxns">iDeal ChIP-seq Kit for Transcription Factors</a></p>
<p><a href="https://www.diagenode.com/en/p/ideal-chip-qpcr-kit">iDeal ChIP qPCR kit</a></p>
</td>
<td style="text-align: center;">
<p><a href="https://www.diagenode.com/en/p/true-microchip-kit-x16-16-rxns">True MicroChIP kit</a></p>
</td>
<td style="text-align: center;">
<p><a href="https://www.diagenode.com/en/p/universal-plant-chip-seq-kit-x24-24-rxns">Universal Plant ChIP-seq kit</a></p>
</td>
</tr>
</tbody>
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<p><em><span style="font-weight: 400;">Table comes from our </span><a href="https://www.diagenode.com/protocols/bioruptor-pico-chromatin-preparation-guide"><span style="font-weight: 400;">Guide for successful chromatin preparation using the Bioruptor® Pico</span></a></em></p>
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<div class="large-12 columns">Diagenode's high yields FFPE DNA extraction using Bioruptor<sup><span>®</span></sup> is a superior method for extracting DNA for Next-Gen Sequencing. Our FFPE DNA Extraction kit contains optimized reagents that are added directly to the FFPE samples to remove paraffin with no toxic reagents, digest tissues, and purify DNA with high yields and low sample degradation. The DNA can then be analyzed by traditional methods or can be sheared with the Bioruptor<sup>®</sup> Pico ultrasonicator for downstream NGS library prep using the MicroPlex Library Preparation Kit.</div>
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<p><span>The 1.5 ml Bioruptor</span><span>® </span><span>Microtubes </span><strong>C30010016 </strong><span>for chromatin shearing strongly improve chromatin sonication efficiency. These tubes have been thoroughly validated for use on the Bioruptor</span><span>® </span><span>Pico (B01060001) and are strongly recommended for DNA and chromatin shearing applications using this instrument. </span></p>
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(int) 1 => array(
'id' => '4011',
'name' => 'Exploring the virulence gene interactome with CRISPR/dCas9 in the humanmalaria parasite.',
'authors' => 'Bryant, JM and Baumgarten, S and Dingli, F and Loew, D and Sinha, A andClaës, A and Preiser, PR and Dedon, PC and Scherf, A',
'description' => '<p>Mutually exclusive expression of the var multigene family is key to immune evasion and pathogenesis in Plasmodium falciparum, but few factors have been shown to play a direct role. We adapted a CRISPR-based proteomics approach to identify novel factors associated with var genes in their natural chromatin context. Catalytically inactive Cas9 ("dCas9") was targeted to var gene regulatory elements, immunoprecipitated, and analyzed with mass spectrometry. Known and novel factors were enriched including structural proteins, DNA helicases, and chromatin remodelers. Functional characterization of PfISWI, an evolutionarily divergent putative chromatin remodeler enriched at the var gene promoter, revealed a role in transcriptional activation. Proteomics of PfISWI identified several proteins enriched at the var gene promoter such as acetyl-CoA synthetase, a putative MORC protein, and an ApiAP2 transcription factor. These findings validate the CRISPR/dCas9 proteomics method and define a new var gene-associated chromatin complex. This study establishes a tool for targeted chromatin purification of unaltered genomic loci and identifies novel chromatin-associated factors potentially involved in transcriptional control and/or chromatin organization of virulence genes in the human malaria parasite.</p>',
'date' => '2020-08-02',
'pmid' => 'http://www.pubmed.gov/32816370',
'doi' => 'https://dx.doi.org/10.15252%2Fmsb.20209569',
'modified' => '2020-12-18 13:26:33',
'created' => '2020-10-12 14:54:59',
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[maximum depth reached]
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(int) 2 => array(
'id' => '3767',
'name' => 'Proteomics Links Ubiquitin Chain Topology Change to Transcription Factor Activation.',
'authors' => 'Li Y, Dammer EB, Gao Y, Lan Q, Villamil MA, Duong DM, Zhang C, Ping L, Lauinger L, Flick K, Xu Z, Wei W, Xing X, Chang L, Jin J, Hong X, Zhu Y, Wu J, Deng Z, He F, Kaiser P, Xu P',
'description' => '<p>A surprising complexity of ubiquitin signaling has emerged with identification of different ubiquitin chain topologies. However, mechanisms of how the diverse ubiquitin codes control biological processes remain poorly understood. Here, we use quantitative whole-proteome mass spectrometry to identify yeast proteins that are regulated by lysine 11 (K11)-linked ubiquitin chains. The entire Met4 pathway, which links cell proliferation with sulfur amino acid metabolism, was significantly affected by K11 chains and selected for mechanistic studies. Previously, we demonstrated that a K48-linked ubiquitin chain represses the transcription factor Met4. Here, we show that efficient Met4 activation requires a K11-linked topology. Mechanistically, our results propose that the K48 chain binds to a topology-selective tandem ubiquitin binding region in Met4 and competes with binding of the basal transcription machinery to the same region. The change to K11-enriched chain architecture releases this competition and permits binding of the basal transcription complex to activate transcription.</p>',
'date' => '2019-08-06',
'pmid' => 'http://www.pubmed.gov/31444107',
'doi' => '10.1016/j.molcel.2019.07.001',
'modified' => '2019-10-03 09:21:23',
'created' => '2019-10-02 16:16:55',
'ProductsPublication' => array(
[maximum depth reached]
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(int) 3 => array(
'id' => '3571',
'name' => 'The role of TCF3 as potential master regulator in blastemal Wilms tumors.',
'authors' => 'Kehl T, Schneider L, Kattler K, Stöckel D, Wegert J, Gerstner N, Ludwig N, Distler U, Tenzer S, Gessler M, Walter J, Keller A, Graf N, Meese E, Lenhof HP',
'description' => '<p>Wilms tumors are the most common type of pediatric kidney tumors. While the overall prognosis for patients is favorable, especially tumors that exhibit a blastemal subtype after preoperative chemotherapy have a poor prognosis. For an improved risk assessment and therapy stratification, it is essential to identify the driving factors that are distinctive for this aggressive subtype. In our study, we compared gene expression profiles of 33 tumor biopsies (17 blastemal and 16 other tumors) after neoadjuvant chemotherapy. The analysis of this dataset using the Regulator Gene Association Enrichment algorithm successfully identified several biomarkers and associated molecular mechanisms that distinguish between blastemal and nonblastemal Wilms tumors. Specifically, regulators involved in embryonic development and epigenetic processes like chromatin remodeling and histone modification play an essential role in blastemal tumors. In this context, we especially identified TCF3 as the central regulatory element. Furthermore, the comparison of ChIP-Seq data of Wilms tumor cell cultures from a blastemal mouse xenograft and a stromal tumor provided further evidence that the chromatin states of blastemal cells share characteristics with embryonic stem cells that are not present in the stromal tumor cell line. These stem-cell like characteristics could potentially add to the increased malignancy and chemoresistance of the blastemal subtype. Along with TCF3, we detected several additional biomarkers that are distinctive for blastemal Wilms tumors after neoadjuvant chemotherapy and that may provide leads for new therapeutic regimens.</p>',
'date' => '2019-03-15',
'pmid' => 'http://www.pubmed.gov/30155889',
'doi' => '10.1002/ijc.31834',
'modified' => '2019-03-21 17:10:17',
'created' => '2019-03-21 14:12:08',
'ProductsPublication' => array(
[maximum depth reached]
)
),
(int) 4 => array(
'id' => '3727',
'name' => 'Transcriptome-wide dynamics of extensive m6A mRNA methylation during Plasmodium falciparum blood-stage development',
'authors' => 'Sebastian Baumgarten, Jessica M. Bryant, Ameya Sinha, Thibaud Reyser, Peter R. Preiser, Peter C. Dedon, Artur Scherf',
'description' => '<p>Malaria pathogenesis results from the asexual replication of Plasmodium falciparum within human red blood cells, which relies on a precisely timed cascade of gene expression over a 48-hour life cycle. Although substantial post-transcriptional regulation of this hardwired program has been observed, it remains unclear how these processes are mediated on a transcriptome-wide level. To this end, we identified mRNA modifications in the P. falciparum transcriptome and performed a comprehensive characterization of N6-methyladenosine (m6A) over the course of blood stage development. Using mass spectrometry and m6A RNA sequencing, we demonstrate that m6A is highly developmentally regulated, exceeding m6A levels known in any other eukaryote. We identify an evolutionarily conserved m6A writer complex and show that knockdown of the putative m6A methyltransferase by CRISPR interference leads to increased levels of transcripts that normally contain m6A. In accordance, we find an inverse correlation between m6A status and mRNA stability or translational efficiency. Our data reveal the crucial role of extensive m6A mRNA methylation in dynamically fine-tuning the transcriptional program of a unicellular eukaryote as well as a new ‘epitranscriptomic’ layer of gene regulation in malaria parasites.</p>',
'date' => '2019-03-09',
'pmid' => 'https://www.nature.com/articles/s41564-019-0521-7',
'doi' => '10.1101/572891.',
'modified' => '2022-05-18 19:27:33',
'created' => '2019-07-31 13:35:50',
'ProductsPublication' => array(
[maximum depth reached]
)
),
(int) 5 => array(
'id' => '3395',
'name' => 'Dot1 promotes H2B ubiquitination by a methyltransferase-independent mechanism.',
'authors' => 'van Welsem T, Korthout T, Ekkebus R, Morais D, Molenaar TM, van Harten K, Poramba-Liyanage DW, Sun SM, Lenstra TL, Srivas R, Ideker T, Holstege FCP, van Attikum H, El Oualid F, Ovaa H, Stulemeijer IJE, Vlaming H, van Leeuwen F',
'description' => '<p>The histone methyltransferase Dot1 is conserved from yeast to human and methylates lysine 79 of histone H3 (H3K79) on the core of the nucleosome. H3K79 methylation by Dot1 affects gene expression and the response to DNA damage, and is enhanced by monoubiquitination of the C-terminus of histone H2B (H2Bub1). To gain more insight into the functions of Dot1, we generated genetic interaction maps of increased-dosage alleles of DOT1. We identified a functional relationship between increased Dot1 dosage and loss of the DUB module of the SAGA co-activator complex, which deubiquitinates H2Bub1 and thereby negatively regulates H3K79 methylation. Increased Dot1 dosage was found to promote H2Bub1 in a dose-dependent manner and this was exacerbated by the loss of SAGA-DUB activity, which also caused a negative genetic interaction. The stimulatory effect on H2B ubiquitination was mediated by the N-terminus of Dot1, independent of methyltransferase activity. Our findings show that Dot1 and H2Bub1 are subject to bi-directional crosstalk and that Dot1 possesses chromatin regulatory functions that are independent of its methyltransferase activity.</p>',
'date' => '2018-09-08',
'pmid' => 'http://www.pubmed.gov/30203048',
'doi' => '10.1093/nar/gky801',
'modified' => '2018-11-09 12:13:19',
'created' => '2018-11-08 12:59:45',
'ProductsPublication' => array(
[maximum depth reached]
)
),
(int) 6 => array(
'id' => '4549',
'name' => 'BET protein inhibition sensitizes glioblastoma cells to temozolomidetreatment by attenuating MGMT expression',
'authors' => 'Tancredi A. et al.',
'description' => '<p>Bromodomain and extra-terminal tail (BET) proteins have been identified as potential epigenetic targets in cancer, including glioblastoma. These epigenetic modifiers link the histone code to gene transcription that can be disrupted with small molecule BET inhibitors (BETi). With the aim of developing rational combination treatments for glioblastoma, we analyzed BETi-induced differential gene expression in glioblastoma derived-spheres, and identified 6 distinct response patterns. To uncover emerging actionable vulnerabilities that can be targeted with a second drug, we extracted the 169 significantly disturbed DNA Damage Response genes and inspected their response pattern. The most prominent candidate with consistent downregulation, was the O-6-methylguanine-DNA methyltransferase (MGMT) gene, a known resistance factor for alkylating agent therapy in glioblastoma. BETi not only reduced MGMT expression in GBM cells, but also inhibited its induction, typically observed upon temozolomide treatment. To determine the potential clinical relevance, we evaluated the specificity of the effect on MGMT expression and MGMT mediated treatment resistance to temozolomide. BETi-mediated attenuation of MGMT expression was associated with reduction of BRD4- and Pol II-binding at the MGMT promoter. On the functional level, we demonstrated that ectopic expression of MGMT under an unrelated promoter was not affected by BETi, while under the same conditions, pharmacologic inhibition of MGMT restored the sensitivity to temozolomide, reflected in an increased level of g-H2AX, a proxy for DNA double-strand breaks. Importantly, expression of MSH6 and MSH2, which are required for sensitivity to unrepaired O6-methylGuanin-lesions, was only briefly affected by BETi. Taken together, the addition of BET-inhibitors to the current standard of care, comprising temozolomide treatment, may sensitize the 50\% of patients whose glioblastoma exert an unmethylated MGMT promoter.</p>',
'date' => '0000-00-00',
'pmid' => 'https://www.researchsquare.com/article/rs-1832996/v1',
'doi' => '10.21203/rs.3.rs-1832996/v1',
'modified' => '2022-11-24 10:06:26',
'created' => '2022-11-24 08:49:52',
'ProductsPublication' => array(
[maximum depth reached]
)
)
),
'Testimonial' => array(),
'Area' => array(),
'SafetySheet' => array()
)
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(int) 11 => 'FR',
(int) 12 => 'DE',
(int) 13 => 'CH',
(int) 14 => 'AT',
(int) 15 => 'ES',
(int) 16 => 'IT',
(int) 17 => 'PT'
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<div class="small-12 columns" >
<h6 style="height:60px">Picoruptor 2 sonication device </h6>
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<h6 style="height:60px">Tube holder for 1.5 ml tubes - Picoruptor</h6>
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'name' => 'BET protein inhibition sensitizes glioblastoma cells to temozolomidetreatment by attenuating MGMT expression',
'authors' => 'Tancredi A. et al.',
'description' => '<p>Bromodomain and extra-terminal tail (BET) proteins have been identified as potential epigenetic targets in cancer, including glioblastoma. These epigenetic modifiers link the histone code to gene transcription that can be disrupted with small molecule BET inhibitors (BETi). With the aim of developing rational combination treatments for glioblastoma, we analyzed BETi-induced differential gene expression in glioblastoma derived-spheres, and identified 6 distinct response patterns. To uncover emerging actionable vulnerabilities that can be targeted with a second drug, we extracted the 169 significantly disturbed DNA Damage Response genes and inspected their response pattern. The most prominent candidate with consistent downregulation, was the O-6-methylguanine-DNA methyltransferase (MGMT) gene, a known resistance factor for alkylating agent therapy in glioblastoma. BETi not only reduced MGMT expression in GBM cells, but also inhibited its induction, typically observed upon temozolomide treatment. To determine the potential clinical relevance, we evaluated the specificity of the effect on MGMT expression and MGMT mediated treatment resistance to temozolomide. BETi-mediated attenuation of MGMT expression was associated with reduction of BRD4- and Pol II-binding at the MGMT promoter. On the functional level, we demonstrated that ectopic expression of MGMT under an unrelated promoter was not affected by BETi, while under the same conditions, pharmacologic inhibition of MGMT restored the sensitivity to temozolomide, reflected in an increased level of g-H2AX, a proxy for DNA double-strand breaks. Importantly, expression of MSH6 and MSH2, which are required for sensitivity to unrepaired O6-methylGuanin-lesions, was only briefly affected by BETi. Taken together, the addition of BET-inhibitors to the current standard of care, comprising temozolomide treatment, may sensitize the 50\% of patients whose glioblastoma exert an unmethylated MGMT promoter.</p>',
'date' => '0000-00-00',
'pmid' => 'https://www.researchsquare.com/article/rs-1832996/v1',
'doi' => '10.21203/rs.3.rs-1832996/v1',
'modified' => '2022-11-24 10:06:26',
'created' => '2022-11-24 08:49:52',
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