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<div class="small-12 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410069-ChIP.jpg" alt="H3K27me3 Antibody for ChIP " caption="false" width="893" height="353" /></center></div>
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<p><small> <strong>Figure 1. ChIP results obtained with the Diagenode antibody directed against H3K27me3</strong><br />ChIP assays were performed using human K562 cells, the Diagenode antibody against H3K27me3 (Cat. No. C15410069) and optimized PCR primer pairs for qPCR. ChIP was performed with the "iDeal ChIP-seq" kit (Cat. No. C01010051), using sheared chromatin from 1 million (figure A) or 100,000 cells (figure B). The indicated amounts of antibody were used per ChIP experiment. IgG (1 µg/IP) was used as a negative IP control. Quantitative PCR was performed with primers specific for the promoter of the active genes GAPDH and EIF4A2, used as negative controls, and TSH2B and MYT1, used as positive controls. The figure shows the recovery, expressed as a % of input (the relative amount of immunoprecipitated DNA compared to input DNA after qPCR analysis).</small></p>
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<p>A. <img src="https://www.diagenode.com/img/product/antibodies/C15410069-ChIP-seq-A.jpg" alt="H3K27me3 Antibody ChIP-seq Grade" caption="false" width="893" height="272" /></p>
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<p>B. <img src="https://www.diagenode.com/img/product/antibodies/C15410069-ChIP-seq-B.jpg" alt="H3K27me3 Antibody for ChIP-seq assay" caption="false" width="893" height="261" /></p>
<p>C. <img src="https://www.diagenode.com/img/product/antibodies/C15410069-ChIP-seq-C.jpg" alt="H3K27me3 Antibody Validated in ChIP-seq" caption="false" width="893" height="191" /></p>
<p>D. <img src="https://www.diagenode.com/img/product/antibodies/C15410069-ChIP-seq-D.jpg" alt="H3K27me3 Antibody for ChIP-seq" caption="false" width="893" height="211" /></p>
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<p><small> <strong>Figure 2. ChIP-seq results obtained with the Diagenode antibody directed against H3K27me3</strong><br />ChIP was performed on sheared chromatin from 100,000 K562 cells using 1 µg of the Diagenode antibody against H3K27me3 (Cat. No. C15410069) as described above. The IP'd DNA was subsequently analysed on an Illumina Genome Analyzer. Library preparation, cluster generation and sequencing were performed according to the manufacturer's instructions. The 36 bp tags were aligned to the human genome using the ELAND algorithm. Figure 2A and B show the signal distribution in two regions surrounding the MYT1 and TSH2B positive control genes, respectively. The position of the PCR amplicon, used for ChIP-qPCR is indicated with an arrow. Figure 2C and D show the signal distribution in two 3 Mb regions from chromosome 11 and 22.</small></p>
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<p><img src="https://www.diagenode.com/img/product/antibodies/C15410069-ELISA.jpg" alt="H3K27me3 Antibody ELISA Validation " caption="false" width="432" height="380" /></p>
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<p><small> <strong>Figure 3. Determination of the antibody titer</strong><br />To determine the titer of the antibody, an ELISA was performed using a serial dilution of the Diagenode antibody against H3K27me3 (Cat. No. C15410069). The antigen used was a peptide containing the histone modification of interest. By plotting the absorbance against the antibody dilution (Figure 3), the titer of the antibody was estimated to be >1:1,000,000.</small></p>
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<p><img src="https://www.diagenode.com/img/product/antibodies/C15410069-dotblot.jpg" alt="H3K27me3 Antibody Dot Blot Validation " caption="false" width="432" height="366" /></p>
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<p><small> <strong>Figure 4. Cross reactivity test of the Diagenode antibody directed against H3K27me3</strong><br />To test the cross reactivity of the Diagenode antibody against H3K27me3 (Cat. No. C15410069), a Dot Blot analysis was performed with peptides containing other modifications or unmodified sequences of histone H3 and H4. One hundred to 0.2 pmol of the respective peptides were spotted on a membrane. The antibody was used at a dilution of 1:20,000. Figure 4A shows a high specificity of the antibody for the modification of interest.</small></p>
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<p><img src="https://www.diagenode.com/img/product/antibodies/C15410069-WB.jpg" alt="H3K27me3 Antibody Validation in Western Blot " caption="false" width="432" height="300" /></p>
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<p><small> <strong>Figure 5. Western blot analysis using the Diagenode antibody directed against H3K27me3</strong><br />Western blot was performed on whole cell (40 µg, lane 1) and histone extracts (15 µg, lane 2) from HeLa cells, and on 1 µg of recombinant histone H2A, H2B, H3 and H4 (lane 3, 4, 5 and 6, respectively) using the Diagenode antibody against H3K27me3 (Cat. No. C15410069). The antibody was diluted 1:1,000 in TBS-Tween containing 5% skimmed milk. The position of the protein of interest is shown on the right, the marker (in kDa) is shown on the left.</small></p>
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<p><img src="https://www.diagenode.com/img/product/antibodies/C15410069-IF.jpg" alt="H3K27me3 Antibody Validation in Immunofluorescence " caption="false" width="700" height="171" /></p>
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<p><small> <strong>Figure 6. Immunofluorescence using the Diagenode antibody directed against H3K27me3</strong><br />HeLa cells were stained with the Diagenode antibody against H3K27me3 (Cat. No. C15410069) and with DAPI. Cells were fixed with 4% formaldehyde for 10’ and blocked with PBS/TX-100 containing 5% normal goat serum and 1% BSA. The cells were immunofluorescently labeled with the H3K27me3 antibody (left) diluted 1:500 in blocking solution followed by an anti-rabbit antibody conjugated to Alexa488. The middle panel shows staining of the nuclei with DAPI. A merge of the two stainings is shown on the right.</small></p>
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<td>ChIP/ChIP-seq <sup>*</sup></td>
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<td>1:5,000</td>
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<td>1:20,000</td>
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<p><small><sup>*</sup> Please note that the optimal antibody amount per IP should be determined by the end-user. We recommend testing 1-5 µg per IP.</small></p>',
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<div class="small-12 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410069-ChIP.jpg" alt="H3K27me3 Antibody for ChIP " caption="false" width="893" height="353" /></center></div>
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<p><small> <strong>Figure 1. ChIP results obtained with the Diagenode antibody directed against H3K27me3</strong><br />ChIP assays were performed using human K562 cells, the Diagenode antibody against H3K27me3 (Cat. No. C15410069) and optimized PCR primer pairs for qPCR. ChIP was performed with the "iDeal ChIP-seq" kit (Cat. No. C01010051), using sheared chromatin from 1 million (figure A) or 100,000 cells (figure B). The indicated amounts of antibody were used per ChIP experiment. IgG (1 µg/IP) was used as a negative IP control. Quantitative PCR was performed with primers specific for the promoter of the active genes GAPDH and EIF4A2, used as negative controls, and TSH2B and MYT1, used as positive controls. The figure shows the recovery, expressed as a % of input (the relative amount of immunoprecipitated DNA compared to input DNA after qPCR analysis).</small></p>
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<div class="small-12 columns">
<p>A. <img src="https://www.diagenode.com/img/product/antibodies/C15410069-ChIP-seq-A.jpg" alt="H3K27me3 Antibody ChIP-seq Grade" caption="false" width="893" height="272" /></p>
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<p>B. <img src="https://www.diagenode.com/img/product/antibodies/C15410069-ChIP-seq-B.jpg" alt="H3K27me3 Antibody for ChIP-seq assay" caption="false" width="893" height="261" /></p>
<p>C. <img src="https://www.diagenode.com/img/product/antibodies/C15410069-ChIP-seq-C.jpg" alt="H3K27me3 Antibody Validated in ChIP-seq" caption="false" width="893" height="191" /></p>
<p>D. <img src="https://www.diagenode.com/img/product/antibodies/C15410069-ChIP-seq-D.jpg" alt="H3K27me3 Antibody for ChIP-seq" caption="false" width="893" height="211" /></p>
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<p><small> <strong>Figure 2. ChIP-seq results obtained with the Diagenode antibody directed against H3K27me3</strong><br />ChIP was performed on sheared chromatin from 100,000 K562 cells using 1 µg of the Diagenode antibody against H3K27me3 (Cat. No. C15410069) as described above. The IP'd DNA was subsequently analysed on an Illumina Genome Analyzer. Library preparation, cluster generation and sequencing were performed according to the manufacturer's instructions. The 36 bp tags were aligned to the human genome using the ELAND algorithm. Figure 2A and B show the signal distribution in two regions surrounding the MYT1 and TSH2B positive control genes, respectively. The position of the PCR amplicon, used for ChIP-qPCR is indicated with an arrow. Figure 2C and D show the signal distribution in two 3 Mb regions from chromosome 11 and 22.</small></p>
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<p><small> <strong>Figure 3. Determination of the antibody titer</strong><br />To determine the titer of the antibody, an ELISA was performed using a serial dilution of the Diagenode antibody against H3K27me3 (Cat. No. C15410069). The antigen used was a peptide containing the histone modification of interest. By plotting the absorbance against the antibody dilution (Figure 3), the titer of the antibody was estimated to be >1:1,000,000.</small></p>
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<div class="row">
<div class="small-6 columns">
<p><img src="https://www.diagenode.com/img/product/antibodies/C15410069-dotblot.jpg" alt="H3K27me3 Antibody Dot Blot Validation " caption="false" width="432" height="366" /></p>
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<div class="small-6 columns">
<p><small> <strong>Figure 4. Cross reactivity test of the Diagenode antibody directed against H3K27me3</strong><br />To test the cross reactivity of the Diagenode antibody against H3K27me3 (Cat. No. C15410069), a Dot Blot analysis was performed with peptides containing other modifications or unmodified sequences of histone H3 and H4. One hundred to 0.2 pmol of the respective peptides were spotted on a membrane. The antibody was used at a dilution of 1:20,000. Figure 4A shows a high specificity of the antibody for the modification of interest.</small></p>
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<div class="row">
<div class="small-6 columns">
<p><img src="https://www.diagenode.com/img/product/antibodies/C15410069-WB.jpg" alt="H3K27me3 Antibody Validation in Western Blot " caption="false" width="432" height="300" /></p>
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<div class="small-6 columns">
<p><small> <strong>Figure 5. Western blot analysis using the Diagenode antibody directed against H3K27me3</strong><br />Western blot was performed on whole cell (40 µg, lane 1) and histone extracts (15 µg, lane 2) from HeLa cells, and on 1 µg of recombinant histone H2A, H2B, H3 and H4 (lane 3, 4, 5 and 6, respectively) using the Diagenode antibody against H3K27me3 (Cat. No. C15410069). The antibody was diluted 1:1,000 in TBS-Tween containing 5% skimmed milk. The position of the protein of interest is shown on the right, the marker (in kDa) is shown on the left.</small></p>
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<div class="row">
<div class="small-12 columns">
<p><img src="https://www.diagenode.com/img/product/antibodies/C15410069-IF.jpg" alt="H3K27me3 Antibody Validation in Immunofluorescence " caption="false" width="700" height="171" /></p>
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<div class="small-12 columns">
<p><small> <strong>Figure 6. Immunofluorescence using the Diagenode antibody directed against H3K27me3</strong><br />HeLa cells were stained with the Diagenode antibody against H3K27me3 (Cat. No. C15410069) and with DAPI. Cells were fixed with 4% formaldehyde for 10’ and blocked with PBS/TX-100 containing 5% normal goat serum and 1% BSA. The cells were immunofluorescently labeled with the H3K27me3 antibody (left) diluted 1:500 in blocking solution followed by an anti-rabbit antibody conjugated to Alexa488. The middle panel shows staining of the nuclei with DAPI. A merge of the two stainings is shown on the right.</small></p>
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'description' => 'Histones are the main constituents of the protein part of chromosomes of eukaryotic cells. They are rich in the amino acids arginine and lysine and have been greatly conserved during evolution. Histones pack the DNA into tight masses of chromatin. Two core histones of each class H2A, H2B, H3 and H4 assemble and are wrapped by 146 base pairs of DNA to form one octameric nucleosome. Histone tails undergo numerous post-translational modifications, which either directly or indirectly alter chromatin structure to facilitate transcriptional activation or repression or other nuclear processes. In addition to the genetic code, combinations of the different histone modifications reveal the so-called “histone code”. Histone methylation and demethylation is dynamically regulated by respectively histone methyl transferases and histone demethylases. Trimethylation of histone H3K27 is associated with gene repression.',
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'reactivity' => 'Human, mouse, rat, pig, zebrafish, Drosophila, Schistosoma, Arabidopsis, cow',
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<thead>
<tr>
<th>Applications</th>
<th>Suggested dilution</th>
<th>References</th>
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<tr>
<td>ChIP/ChIP-seq <sup>*</sup></td>
<td>1 µg/ChIP</td>
<td>Fig 1, 2</td>
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<tr>
<td>ELISA</td>
<td>1:5,000</td>
<td>Fig 3</td>
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<tr>
<td>Dot Blotting</td>
<td>1:20,000</td>
<td>Fig 4</td>
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<tr>
<td>Western Blotting</td>
<td>1:1,000</td>
<td>Fig 5</td>
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<tr>
<td>Immunofluorescence</td>
<td>1:500</td>
<td>Fig 6</td>
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<p><small><sup>*</sup> Please note that the optimal antibody amount per IP should be determined by the end-user. We recommend testing 1-5 µg per IP.</small></p>',
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'name' => 'H3K27me3 Antibody',
'description' => '<p><span>Polyclonal antibody raised in rabbit against against histone <strong>H3, trimethylated at lysine 27</strong> (<strong>H3K27me3</strong>), using a KLH-conjugated synthetic peptide.</span></p>',
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<div class="small-12 columns"><center><img src="https://www.diagenode.com/img/product/antibodies/C15410069-ChIP.jpg" alt="H3K27me3 Antibody for ChIP " style="display: block; margin-left: auto; margin-right: auto;" /></center></div>
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<p><small> <strong>Figure 1. ChIP results obtained with the Diagenode antibody directed against H3K27me3</strong><br />ChIP assays were performed using human K562 cells, the Diagenode antibody against H3K27me3 (Cat. No. C15410069) and optimized PCR primer pairs for qPCR. ChIP was performed with the "iDeal ChIP-seq" kit (Cat. No. C01010051), using sheared chromatin from 1 million (figure A) or 100,000 cells (figure B). The indicated amounts of antibody were used per ChIP experiment. IgG (1 µg/IP) was used as a negative IP control. Quantitative PCR was performed with primers specific for the promoter of the active genes GAPDH and EIF4A2, used as negative controls, and TSH2B and MYT1, used as positive controls. The figure shows the recovery, expressed as a % of input (the relative amount of immunoprecipitated DNA compared to input DNA after qPCR analysis).</small></p>
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<div class="small-12 columns">
<p>A. <img src="https://www.diagenode.com/img/product/antibodies/C15410069-ChIP-seq-A.jpg" alt="H3K27me3 Antibody ChIP-seq Grade" style="display: block; margin-left: auto; margin-right: auto;" /></p>
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<p>B. <img src="https://www.diagenode.com/img/product/antibodies/C15410069-ChIP-seq-B.jpg" alt="H3K27me3 Antibody for ChIP-seq assay" style="display: block; margin-left: auto; margin-right: auto;" /></p>
<p>C. <img src="https://www.diagenode.com/img/product/antibodies/C15410069-ChIP-seq-C.jpg" alt="H3K27me3 Antibody Validated in ChIP-seq" style="display: block; margin-left: auto; margin-right: auto;" /></p>
<p>D. <img src="https://www.diagenode.com/img/product/antibodies/C15410069-ChIP-seq-D.jpg" alt="H3K27me3 Antibody for ChIP-seq" style="display: block; margin-left: auto; margin-right: auto;" /></p>
</div>
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<div class="row">
<div class="small-12 columns">
<p><small> <strong>Figure 2. ChIP-seq results obtained with the Diagenode antibody directed against H3K27me3</strong><br />ChIP was performed on sheared chromatin from 100,000 K562 cells using 1 µg of the Diagenode antibody against H3K27me3 (Cat. No. C15410069) as described above. The IP'd DNA was subsequently analysed on an Illumina Genome Analyzer. Library preparation, cluster generation and sequencing were performed according to the manufacturer's instructions. The 36 bp tags were aligned to the human genome using the ELAND algorithm. Figure 2A and B show the signal distribution in two regions surrounding the MYT1 and TSH2B positive control genes, respectively. The position of the PCR amplicon, used for ChIP-qPCR is indicated with an arrow. Figure 2C and D show the signal distribution in two 3 Mb regions from chromosome 11 and 22.</small></p>
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<div class="small-6 columns">
<p><small> <strong>Figure 3. Determination of the antibody titer</strong><br />To determine the titer of the antibody, an ELISA was performed using a serial dilution of the Diagenode antibody against H3K27me3 (Cat. No. C15410069). The antigen used was a peptide containing the histone modification of interest. By plotting the absorbance against the antibody dilution (Figure 3), the titer of the antibody was estimated to be >1:1,000,000.</small></p>
</div>
</div>
<div class="row">
<div class="small-6 columns">
<p><img src="https://www.diagenode.com/img/product/antibodies/C15410069-dotblot.jpg" alt="H3K27me3 Antibody Dot Blot Validation " style="display: block; margin-left: auto; margin-right: auto;" /></p>
</div>
<div class="small-6 columns">
<p><small> <strong>Figure 4. Cross reactivity test of the Diagenode antibody directed against H3K27me3</strong><br />To test the cross reactivity of the Diagenode antibody against H3K27me3 (Cat. No. C15410069), a Dot Blot analysis was performed with peptides containing other modifications or unmodified sequences of histone H3 and H4. One hundred to 0.2 pmol of the respective peptides were spotted on a membrane. The antibody was used at a dilution of 1:20,000. Figure 4A shows a high specificity of the antibody for the modification of interest.</small></p>
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</div>
<div class="row">
<div class="small-6 columns">
<p><img src="https://www.diagenode.com/img/product/antibodies/C15410069-WB.jpg" alt="H3K27me3 Antibody Validation in Western Blot " style="display: block; margin-left: auto; margin-right: auto;" /></p>
</div>
<div class="small-6 columns">
<p><small> <strong>Figure 5. Western blot analysis using the Diagenode antibody directed against H3K27me3</strong><br />Western blot was performed on whole cell (40 µg, lane 1) and histone extracts (15 µg, lane 2) from HeLa cells, and on 1 µg of recombinant histone H2A, H2B, H3 and H4 (lane 3, 4, 5 and 6, respectively) using the Diagenode antibody against H3K27me3 (Cat. No. C15410069). The antibody was diluted 1:1,000 in TBS-Tween containing 5% skimmed milk. The position of the protein of interest is shown on the right, the marker (in kDa) is shown on the left.</small></p>
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</div>
<div class="row">
<div class="small-12 columns">
<p><img src="https://www.diagenode.com/img/product/antibodies/C15410069-IF.jpg" alt="H3K27me3 Antibody Validation in Immunofluorescence " style="display: block; margin-left: auto; margin-right: auto;" /></p>
</div>
</div>
<div class="row">
<div class="small-12 columns">
<p><small> <strong>Figure 6. Immunofluorescence using the Diagenode antibody directed against H3K27me3</strong><br />HeLa cells were stained with the Diagenode antibody against H3K27me3 (Cat. No. C15410069) and with DAPI. Cells were fixed with 4% formaldehyde for 10’ and blocked with PBS/TX-100 containing 5% normal goat serum and 1% BSA. The cells were immunofluorescently labeled with the H3K27me3 antibody (left) diluted 1:500 in blocking solution followed by an anti-rabbit antibody conjugated to Alexa488. The middle panel shows staining of the nuclei with DAPI. A merge of the two stainings is shown on the right.</small></p>
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<p>Learn more about: <a href="https://www.diagenode.com/applications/western-blot">Loading control, MW marker visualization</a><em>. <br /></em></p>
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<p><sup><strong>Immunofluorescence using the Diagenode monoclonal antibody directed against CRISPR/Cas9</strong></sup></p>
<p><sup>HeLa cells transfected with a Cas9 expression vector (left) or untransfected cells (right) were fixed in methanol at -20°C, permeabilized with acetone at -20°C and blocked with PBS containing 2% BSA. The cells were stained with the Cas9 C-terminal antibody (Cat. No. C15200229) diluted 1:400, followed by incubation with an anti-mouse secondary antibody coupled to AF488. The bottom images show counter-staining of the nuclei with Hoechst 33342.</sup></p>
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'description' => '<p>Histones are the main protein components of chromatin involved in the compaction of DNA into nucleosomes, the basic units of chromatin. A <strong>nucleosome</strong> consists of one pair of each of the core histones (<strong>H2A</strong>, <strong>H2B</strong>, <strong>H3</strong> and <strong>H4</strong>) forming an octameric structure wrapped by 146 base pairs of DNA. The different nucleosomes are linked by the linker histone<strong> H1, </strong>allowing for further condensation of chromatin.</p>
<p>The core histones have a globular structure with large unstructured N-terminal tails protruding from the nucleosome. They can undergo to multiple post-translational modifications (PTM), mainly at the N-terminal tails. These <strong>post-translational modifications </strong>include methylation, acetylation, phosphorylation, ubiquitinylation, citrullination, sumoylation, deamination and crotonylation. The most well characterized PTMs are <strong>methylation,</strong> <strong>acetylation and phosphorylation</strong>. Histone methylation occurs mainly on lysine (K) residues, which can be mono-, di- or tri-methylated, and on arginines (R), which can be mono-methylated and symmetrically or asymmetrically di-methylated. Histone acetylation occurs on lysines and histone phosphorylation mainly on serines (S), threonines (T) and tyrosines (Y).</p>
<p>The PTMs of the different residues are involved in numerous processes such as DNA repair, DNA replication and chromosome condensation. They influence the chromatin organization and can be positively or negatively associated with gene expression. Trimethylation of H3K4, H3K36 and H3K79, and lysine acetylation generally result in an open chromatin configuration (figure below) and are therefore associated with <strong>euchromatin</strong> and gene activation. Trimethylation of H3K9, K3K27 and H4K20, on the other hand, is enriched in <strong>heterochromatin </strong>and associated with gene silencing. The combination of different histone modifications is called the "<strong>histone code</strong>”, analogous to the genetic code.</p>
<p><img src="https://www.diagenode.com/img/categories/antibodies/histone-marks-illustration.png" /></p>
<p>Diagenode is proud to offer a large range of antibodies against histones and histone modifications. Our antibodies are highly specific and have been validated in many applications, including <strong>ChIP</strong> and <strong>ChIP-seq</strong>.</p>
<p>Diagenode’s collection includes antibodies recognizing:</p>
<ul>
<li><strong>Histone H1 variants</strong></li>
<li><strong>Histone H2A, H2A variants and histone H2A</strong> <strong>modifications</strong> (serine phosphorylation, lysine acetylation, lysine ubiquitinylation)</li>
<li><strong>Histone H2B and H2B</strong> <strong>modifications </strong>(serine phosphorylation, lysine acetylation)</li>
<li><strong>Histone H3 and H3 modifications </strong>(lysine methylation (mono-, di- and tri-methylated), lysine acetylation, serine phosphorylation, threonine phosphorylation, arginine methylation (mono-methylated, symmetrically and asymmetrically di-methylated))</li>
<li><strong>Histone H4 and H4 modifications (</strong>lysine methylation (mono-, di- and tri-methylated), lysine acetylation, arginine methylation (mono-methylated and symmetrically di-methylated), serine phosphorylation )</li>
</ul>
<p><span style="font-weight: 400;"><strong>HDAC's HAT's, HMT's and other</strong> <strong>enzymes</strong> which modify histones can be found in the category <a href="../categories/chromatin-modifying-proteins-histone-transferase">Histone modifying enzymes</a><br /></span></p>
<p><span style="font-weight: 400;"> Diagenode’s highly validated antibodies:</span></p>
<ul>
<li><span style="font-weight: 400;"> Highly sensitive and specific</span></li>
<li><span style="font-weight: 400;"> Cost-effective (requires less antibody per reaction)</span></li>
<li><span style="font-weight: 400;"> Batch-specific data is available on the website</span></li>
<li><span style="font-weight: 400;"> Expert technical support</span></li>
<li><span style="font-weight: 400;"> Sample sizes available</span></li>
<li><span style="font-weight: 400;"> 100% satisfaction guarantee</span></li>
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'meta_description' => 'Polyclonal and Monoclonal Antibodies against Histones and their modifications validated for many applications, including Chromatin Immunoprecipitation (ChIP) and ChIP-Sequencing (ChIP-seq)',
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'description' => '<p><span style="font-weight: 400;">All Diagenode’s antibodies are listed below. Please, use our Quick search field to find the antibody of interest by target name, application, purity.</span></p>
<p><span style="font-weight: 400;">Diagenode’s highly validated antibodies:</span></p>
<ul>
<li>Highly sensitive and specific</li>
<li>Cost-effective (requires less antibody per reaction)</li>
<li>Batch-specific data is available on the website</li>
<li>Expert technical support</li>
<li>Sample sizes available</li>
<li>100% satisfaction guarantee</li>
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'meta_description' => 'Diagenode Offers Strict quality standards with Rigorous QC and validated Antibodies. Classified based on level of validation for flexibility of Application. Comprehensive selection of histone and non-histone Antibodies',
'meta_title' => 'Diagenode's selection of Antibodies is exclusively dedicated for Epigenetic Research | Diagenode',
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'name' => 'ChIP-grade antibodies',
'description' => '<div class="row">
<div class="small-12 columns"><center></center>
<p><br />Chromatin immunoprecipitation (<b>ChIP</b>) is a technique to study the associations of proteins with the specific genomic regions in intact cells. One of the most important steps of this protocol is the immunoprecipitation of targeted protein using the antibody specifically recognizing it. The quality of antibodies used in ChIP is essential for the success of the experiment. Diagenode offers extensively validated ChIP-grade antibodies, confirmed for their specificity, and high level of performance in ChIP. Each batch is validated, and batch-specific data are available on the website.</p>
<p></p>
</div>
</div>
<p><strong>ChIP results</strong> obtained with the antibody directed against H3K4me3 (Cat. No. <a href="../p/h3k4me3-polyclonal-antibody-premium-50-ug-50-ul">C15410003</a>). </p>
<div class="row">
<div class="small-12 medium-6 large-6 columns"><img src="https://www.diagenode.com/img/product/antibodies/C15410003-fig1-ChIP.jpg" alt="" width="400" height="315" /> </div>
<div class="small-12 medium-6 large-6 columns">
<p></p>
<p></p>
<p></p>
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</div>
<p></p>
<p>Our aim at Diagenode is to offer the largest collection of highly specific <strong>ChIP-grade antibodies</strong>. We add new antibodies monthly. Find your ChIP-grade antibody in the list below and check more information about tested applications, extensive validation data, and product information.</p>',
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'meta_description' => 'Diagenode Offers Extensively Validated ChIP-Grade Antibodies, Confirmed for their Specificity, and high level of Performance in Chromatin Immunoprecipitation ChIP',
'meta_title' => 'Chromatin immunoprecipitation ChIP-grade antibodies | Diagenode',
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'description' => '<p><b>Unparalleled ChIP-Seq results with the most rigorously validated antibodies</b></p>
<p><span style="font-weight: 400;">Diagenode provides leading solutions for epigenetic research. Because ChIP-seq is a widely-used technique, we validate our antibodies in ChIP and ChIP-seq experiments (in addition to conventional methods like Western blot, Dot blot, ELISA, and immunofluorescence) to provide the highest quality antibody. We standardize our validation and production to guarantee high product quality without technical bias. Diagenode guarantees ChIP-seq grade antibody performance under our suggested conditions.</span></p>
<div class="row">
<div class="small-12 medium-9 large-9 columns">
<p><strong>ChIP-seq profile</strong> of active (H3K4me3 and H3K36me3) and inactive (H3K27me3) marks using Diagenode antibodies.</p>
<img src="https://www.diagenode.com/img/categories/antibodies/chip-seq-grade-antibodies.png" /></div>
<div class="small-12 medium-3 large-3 columns">
<p><small> ChIP was performed on sheared chromatin from 100,000 K562 cells using iDeal ChIP-seq kit for Histones (cat. No. C01010051) with 1 µg of the Diagenode antibodies against H3K27me3 (cat. No. C15410195) and H3K4me3 (cat. No. C15410003), and 0.5 µg of the antibody against H3K36me3 (cat. No. C15410192). The IP'd DNA was subsequently analysed on an Illumina Genome Analyzer. Library preparation, cluster generation and sequencing were performed according to the manufacturer's instructions. The 36 bp tags were aligned to the human genome using the ELAND algorithm. The figure shows the signal distribution along the complete sequence of human chromosome 3, a zoomin to a 10 Mb region and a further zoomin to a 1.5 Mb region. </small></p>
</div>
</div>
<p>Diagenode’s highly validated antibodies:</p>
<ul>
<li>Highly sensitive and specific</li>
<li>Cost-effective (requires less antibody per reaction)</li>
<li>Batch-specific data is available on the website</li>
<li>Expert technical support</li>
<li>Sample sizes available</li>
<li>100% satisfaction guarantee</li>
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'meta_title' => 'Chromatin Immunoprecipitation ChIP-Seq Grade Antibodies | Diagenode',
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'description' => '<h1><strong>Validated epigenetics antibodies</strong> – care for a sample?<br /> </h1>
<p>Diagenode has partnered with leading epigenetics experts and numerous epigenetics consortiums to bring to you a validated and comprehensive collection of epigenetic antibodies. As an expert in epigenetics, we are committed to offering highly-specific antibodies validated for ChIP/ChIP-seq and many other applications. All batch-specific validation data is available on our website.<br /><a href="../categories/antibodies">Read about our expertise in antibody production</a>.</p>
<ul>
<li><strong>Focused</strong> - Diagenode's selection of antibodies is exclusively dedicated for epigenetic research. <a title="See the full collection." href="../categories/all-antibodies">See the full collection.</a></li>
<li><strong>Strict quality standards</strong> with rigorous QC and validation</li>
<li><strong>Classified</strong> based on level of validation for flexibility of application</li>
</ul>
<p>Existing sample sizes are listed below. We will soon expand our collection. Are you looking for a sample size of another antibody? Just <a href="mailto:agnieszka.zelisko@diagenode.com?Subject=Sample%20Size%20Request" target="_top">Contact us</a>.</p>',
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'description' => '<p style="text-align: justify;"><span>Epigenetic research tools have evolved over time from endpoint PCR to qPCR to the analyses of large sets of genome-wide sequencing data. ChIP sequencing (ChIP-seq) has now become the gold standard method for chromatin studies, given the accuracy and coverage scale of the approach over other methods. Successful ChIP-seq, however, requires a higher level of experimental accuracy and consistency in all steps of ChIP than ever before. Particularly crucial is the quality of ChIP antibodies. </span></p>',
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'id' => '4952',
'name' => 'Epigenetic alterations affecting hematopoietic regulatory networks as drivers of mixed myeloid/lymphoid leukemia',
'authors' => 'Roger Mulet-Lazaro et al.',
'description' => '<p><span>Leukemias with ambiguous lineage comprise several loosely defined entities, often without a clear mechanistic basis. Here, we extensively profile the epigenome and transcriptome of a subgroup of such leukemias with CpG Island Methylator Phenotype. These leukemias exhibit comparable hybrid myeloid/lymphoid epigenetic landscapes, yet heterogeneous genetic alterations, suggesting they are defined by their shared epigenetic profile rather than common genetic lesions. Gene expression enrichment reveals similarity with early T-cell precursor acute lymphoblastic leukemia and a lymphoid progenitor cell of origin. In line with this, integration of differential DNA methylation and gene expression shows widespread silencing of myeloid transcription factors. Moreover, binding sites for hematopoietic transcription factors, including CEBPA, SPI1 and LEF1, are uniquely inaccessible in these leukemias. Hypermethylation also results in loss of CTCF binding, accompanied by changes in chromatin interactions involving key transcription factors. In conclusion, epigenetic dysregulation, and not genetic lesions, explains the mixed phenotype of this group of leukemias with ambiguous lineage. The data collected here constitute a useful and comprehensive epigenomic reference for subsequent studies of acute myeloid leukemias, T-cell acute lymphoblastic leukemias and mixed-phenotype leukemias.</span></p>',
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'name' => 'Master corepressor inactivation through multivalent SLiM-induced polymerization mediated by the oncogene suppressor RAI2',
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'description' => '<p><span>While the elucidation of regulatory mechanisms of folded proteins is facilitated due to their amenability to high-resolution structural characterization, investigation of these mechanisms in disordered proteins is more challenging due to their structural heterogeneity, which can be captured by a variety of biophysical approaches. Here, we used the transcriptional master corepressor CtBP, which binds the putative metastasis suppressor RAI2 through repetitive SLiMs, as a model system. Using cryo-electron microscopy embedded in an integrative structural biology approach, we show that RAI2 unexpectedly induces CtBP polymerization through filaments of stacked tetrameric CtBP layers. These filaments lead to RAI2-mediated CtBP nuclear foci and relieve its corepressor function in RAI2-expressing cancer cells. The impact of RAI2-mediated CtBP loss-of-function is illustrated by the analysis of a diverse cohort of prostate cancer patients, which reveals a substantial decrease in RAI2 in advanced treatment-resistant cancer subtypes. As RAI2-like SLiM motifs are found in a wide range of organisms, including pathogenic viruses, our findings serve as a paradigm for diverse functional effects through multivalent interaction-mediated polymerization by disordered proteins in healthy and diseased conditions.</span></p>',
'date' => '2024-06-19',
'pmid' => 'https://www.nature.com/articles/s41467-024-49488-3',
'doi' => 'https://doi.org/10.1038/s41467-024-49488-3',
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'id' => '4950',
'name' => 'Master corepressor inactivation through multivalent SLiM-induced polymerization mediated by the oncogene suppressor RAI2',
'authors' => 'Nishit Goradia et al.',
'description' => '<p><span>While the elucidation of regulatory mechanisms of folded proteins is facilitated due to their amenability to high-resolution structural characterization, investigation of these mechanisms in disordered proteins is more challenging due to their structural heterogeneity, which can be captured by a variety of biophysical approaches. Here, we used the transcriptional master corepressor CtBP, which binds the putative metastasis suppressor RAI2 through repetitive SLiMs, as a model system. Using cryo-electron microscopy embedded in an integrative structural biology approach, we show that RAI2 unexpectedly induces CtBP polymerization through filaments of stacked tetrameric CtBP layers. These filaments lead to RAI2-mediated CtBP nuclear foci and relieve its corepressor function in RAI2-expressing cancer cells. The impact of RAI2-mediated CtBP loss-of-function is illustrated by the analysis of a diverse cohort of prostate cancer patients, which reveals a substantial decrease in RAI2 in advanced treatment-resistant cancer subtypes. As RAI2-like SLiM motifs are found in a wide range of organisms, including pathogenic viruses, our findings serve as a paradigm for diverse functional effects through multivalent interaction-mediated polymerization by disordered proteins in healthy and diseased conditions.</span></p>',
'date' => '2024-06-19',
'pmid' => 'https://www.nature.com/articles/s41467-024-49488-3',
'doi' => ' https://doi.org/10.1038/s41467-024-49488-3',
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'id' => '4791',
'name' => 'Distinct regulation of EZH2 and its repressive H3K27me3 mark inPolyomavirus -positive and -negative Merkel cell carcinoma.',
'authors' => 'Durand M-A et al.',
'description' => '<p>Merkel cell carcinoma (MCC) is an aggressive skin cancer for which Merkel cell polyomavirus (MCPyV) integration and expression of viral oncogenes small T and Large T have been identified as major oncogenic determinants. Recently, a component of the PRC2 complex, the histone methyltransferase EZH2 that induces H3K27 tri-methylation as a repressive mark has been proposed as a potential therapeutic target in MCC. Since divergent results have been reported for the levels of EZH2 and H3K27me3, we analyzed these factors in a large MCC cohort to identify the molecular determinants of EZH2 activity in MCC and to establish MCC cell lines sensitivity to EZH2 inhibitors. Immunohistochemical expression of EZH2 was observed in 92\% of MCC tumors (156/170) with higher expression levels in virus-positive than virus-negative tumors (p= 0.026). For the latter, we demonstrated overexpression of EZHIP, a negative regulator of the PRC2 complex. In vitro, ectopic expression of the Large T antigen in fibroblasts led to the induction of EZH2 expression while knockdown of T antigens in MCC cell lines resulted in decreased EZH2 expression. EZH2 inhibition led to selective cytotoxicity on virus-positive MCC cell lines. This study highlights the distinct mechanisms of EZH2 induction between virus-negative and -positive MCC.</p>',
'date' => '2023-04-01',
'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/37037414',
'doi' => '10.1016/j.jid.2023.02.038',
'modified' => '2023-06-12 09:05:58',
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'id' => '4605',
'name' => 'Gene Regulatory Interactions at Lamina-Associated Domains',
'authors' => 'Madsen-Østerbye J. et al.',
'description' => '<p>The nuclear lamina provides a repressive chromatin environment at the nuclear periphery. However, whereas most genes in lamina-associated domains (LADs) are inactive, over ten percent reside in local euchromatic contexts and are expressed. How these genes are regulated and whether they are able to interact with regulatory elements remain unclear. Here, we integrate publicly available enhancer-capture Hi-C data with our own chromatin state and transcriptomic datasets to show that inferred enhancers of active genes in LADs are able to form connections with other enhancers within LADs and outside LADs. Fluorescence in situ hybridization analyses show proximity changes between differentially expressed genes in LADs and distant enhancers upon the induction of adipogenic differentiation. We also provide evidence of involvement of lamin A/C, but not lamin B1, in repressing genes at the border of an in-LAD active region within a topological domain. Our data favor a model where the spatial topology of chromatin at the nuclear lamina is compatible with gene expression in this dynamic nuclear compartment.</p>',
'date' => '2023-01-01',
'pmid' => 'https://doi.org/10.3390%2Fgenes14020334',
'doi' => '10.3390/genes14020334',
'modified' => '2023-04-04 08:57:32',
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'id' => '4454',
'name' => 'Histone lysine demethylase inhibition reprograms prostate cancermetabolism and mechanics.',
'authors' => 'Chianese Ugo and Papulino Chiara and Passaro Eugenia andEvers Tom Mj and Babaei Mehrad and Toraldo Antonella andDe Marchi Tommaso and Niméus Emma and Carafa Vincenzo andNicoletti Maria Maddalena and Del Gaudio Nunzio andIaccarino Nunzia an',
'description' => '<p>OBJECTIVE: Aberrant activity of androgen receptor (AR) is the primary cause underlying development and progression of prostate cancer (PCa) and castration-resistant PCa (CRPC). Androgen signaling regulates gene transcription and lipid metabolism, facilitating tumor growth and therapy resistance in early and advanced PCa. Although direct AR signaling inhibitors exist, AR expression and function can also be epigenetically regulated. Specifically, lysine (K)-specific demethylases (KDMs), which are often overexpressed in PCa and CRPC phenotypes, regulate the AR transcriptional program. METHODS: We investigated LSD1/UTX inhibition, two KDMs, in PCa and CRPC using a multi-omics approach. We first performed a mitochondrial stress test to evaluate respiratory capacity after treatment with MC3324, a dual KDM-inhibitor, and then carried out lipidomic, proteomic, and metabolic analyses. We also investigated mechanical cellular properties with acoustic force spectroscopy. RESULTS: MC3324 induced a global increase in H3K4me2 and H3K27me3 accompanied by significant growth arrest and apoptosis in androgen-responsive and -unresponsive PCa systems. LSD1/UTX inhibition downregulated AR at both transcriptional and non-transcriptional level, showing cancer selectivity, indicating its potential use in resistance to androgen deprivation therapy. Since MC3324 impaired metabolic activity, by modifying the protein and lipid content in PCa and CRPC cell lines. Epigenetic inhibition of LSD1/UTX disrupted mitochondrial ATP production and mediated lipid plasticity, which affected the phosphocholine class, an important structural element for the cell membrane in PCa and CRPC associated with changes in physical and mechanical properties of cancer cells. CONCLUSIONS: Our data suggest a network in which epigenetics, hormone signaling, metabolite availability, lipid content, and mechano-metabolic process are closely related. This network may be able to identify additional hotspots for pharmacological intervention and underscores the key role of KDM-mediated epigenetic modulation in PCa and CRPC.</p>',
'date' => '2022-08-01',
'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/35944897',
'doi' => '10.1016/j.molmet.2022.101561',
'modified' => '2022-10-21 09:37:56',
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'id' => '4514',
'name' => 'Histone H3K36me2 and H3K36me3 form a chromatin platform essentialfor DNMT3A-dependent DNA methylation in mouse oocytes.',
'authors' => 'Yano Seiichi at al.',
'description' => '<p>Establishment of the DNA methylation landscape of mammalian oocytes, mediated by the DNMT3A-DNMT3L complex, is crucial for reproduction and development. In mouse oocytes, high levels of DNA methylation occur exclusively in the transcriptionally active regions, with moderate to low levels of methylation in other regions. Histone H3K36me3 mediates the high levels of methylation in the transcribed regions; however, it is unknown which histone mark guides the methylation in the other regions. Here, we show that, in mouse oocytes, H3K36me2 is highly enriched in the X chromosome and is broadly distributed across all autosomes. Upon H3K36me2 depletion, DNA methylation in moderately methylated regions is selectively affected, and a methylation pattern unique to the X chromosome is switched to an autosome-like pattern. Furthermore, we find that simultaneous depletion of H3K36me2 and H3K36me3 results in global hypomethylation, comparable to that of DNMT3A depletion. Therefore, the two histone marks jointly provide the chromatin platform essential for guiding DNMT3A-dependent DNA methylation in mouse oocytes.</p>',
'date' => '2022-08-01',
'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/35922445',
'doi' => '10.1038/s41467-022-32141-2',
'modified' => '2022-11-24 08:41:31',
'created' => '2022-11-15 09:26:20',
'ProductsPublication' => array(
[maximum depth reached]
)
),
(int) 7 => array(
'id' => '4417',
'name' => 'HOTAIR interacts with PRC2 complex regulating the regional preadipocytetranscriptome and human fat distribution.',
'authors' => 'Kuo Feng-Chih et al.',
'description' => '<p>Mechanisms governing regional human adipose tissue (AT) development remain undefined. Here, we show that the long non-coding RNA HOTAIR (HOX transcript antisense RNA) is exclusively expressed in gluteofemoral AT, where it is essential for adipocyte development. We find that HOTAIR interacts with polycomb repressive complex 2 (PRC2) and we identify core HOTAIR-PRC2 target genes involved in adipocyte lineage determination. Repression of target genes coincides with PRC2 promoter occupancy and H3K27 trimethylation. HOTAIR is also involved in modifying the gluteal adipocyte transcriptome through alternative splicing. Gluteal-specific expression of HOTAIR is maintained by defined regions of open chromatin across the HOTAIR promoter. HOTAIR expression levels can be modified by hormonal (estrogen, glucocorticoids) and genetic variation (rs1443512 is a HOTAIR eQTL associated with reduced gynoid fat mass). These data identify HOTAIR as a dynamic regulator of the gluteal adipocyte transcriptome and epigenome with functional importance for human regional AT development.</p>',
'date' => '2022-07-01',
'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/35905723',
'doi' => '10.1016/j.celrep.2022.111136',
'modified' => '2022-09-27 14:41:23',
'created' => '2022-09-08 16:32:20',
'ProductsPublication' => array(
[maximum depth reached]
)
),
(int) 8 => array(
'id' => '4220',
'name' => 'Effects of GSK-J4 on JMJD3 Histone Demethylase in Mouse Prostate Cancer Xenografts',
'authors' => 'Sanchez A. et al.',
'description' => '<p><strong class="sub-title">Background/aim:<span> </span></strong>Histone methylation status is required to control gene expression. H3K27me3 is an epigenetic tri-methylation modification to histone H3 controlled by the demethylase JMJD3. JMJD3 is dysregulated in a wide range of cancers and has been shown to control the expression of a specific growth-modulatory gene signature, making it an interesting candidate to better understand prostate tumor progression in vivo. This study aimed to identify the impact of JMJD3 inhibition by its inhibitor, GSK4, on prostate tumor growth in vivo.</p>
<p><strong class="sub-title">Materials and methods:<span> </span></strong>Prostate cancer cell lines were implanted into Balb/c nude male mice. The effects of the selective JMJD3 inhibitor GSK-J4 on tumor growth were analyzed by bioluminescence assays and H3K27me3-regulated changes in gene expression were analyzed by ChIP-qPCR and RT-qPCR.</p>
<p><strong class="sub-title">Results:<span> </span></strong>JMJD3 inhibition contributed to an increase in tumor growth in androgen-independent (AR-) xenografts and a decrease in androgen-dependent (AR+). GSK-J4 treatment modulated H3K27me3 enrichment on the gene panel in DU-145-luc xenografts while it had little effect on PC3-luc and no effect on LNCaP-luc. Effects of JMJD3 inhibition affected the panel gene expression.</p>
<p><strong class="sub-title">Conclusion:<span> </span></strong>JMJD3 has a differential effect in prostate tumor progression according to AR status. Our results suggest that JMJD3 is able to play a role independently of its demethylase function in androgen-independent prostate cancer. The effects of GSK-J4 on AR+ prostate xenografts led to a decrease in tumor growth.</p>',
'date' => '2022-05-01',
'pmid' => 'https://pubmed.ncbi.nlm.nih.gov/35430567/',
'doi' => '10.21873/cgp.20324',
'modified' => '2022-04-21 11:54:21',
'created' => '2022-04-21 11:54:21',
'ProductsPublication' => array(
[maximum depth reached]
)
),
(int) 9 => array(
'id' => '4221',
'name' => 'Epigenetic Mechanisms Mediating Cell State Transitions in Chondrocytes',
'authors' => 'Wuelling M. et al.',
'description' => '<p><span>Epigenetic modifications play critical roles in regulating cell lineage differentiation, but the epigenetic mechanisms guiding specific differentiation steps within a cell lineage have rarely been investigated. To decipher such mechanisms, we used the defined transition from proliferating (PC) into hypertrophic chondrocytes (HC) during endochondral ossification as a model. We established a map of activating and repressive histone modifications for each cell type. ChromHMM state transition analysis and Pareto-based integration of differential levels of mRNA and epigenetic marks revealed that differentiation-associated gene repression is initiated by the addition of H3K27me3 to promoters still carrying substantial levels of activating marks. Moreover, the integrative analysis identified genes specifically expressed in cells undergoing the transition into hypertrophy. Investigation of enhancer profiles detected surprising differences in enhancer number, location, and transcription factor binding sites between the two closely related cell types. Furthermore, cell type-specific upregulation of gene expression was associated with increased numbers of H3K27ac peaks. Pathway analysis identified PC-specific enhancers associated with chondrogenic genes, whereas HC-specific enhancers mainly control metabolic pathways linking epigenetic signature to biological functions. Since HC-specific enhancers show a higher conservation in postnatal tissues, the switch to metabolic pathways seems to be a hallmark of differentiated tissues. Surprisingly, the analysis of H3K27ac levels at super-enhancers revealed a rapid adaption of H3K27ac occupancy to changes in gene expression, supporting the importance of enhancer modulation for acute alterations in gene expression. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).</span></p>',
'date' => '2022-05-01',
'pmid' => 'https://pubmed.ncbi.nlm.nih.gov/33534175/',
'doi' => '10.1002/jbmr.4263',
'modified' => '2022-04-25 11:46:32',
'created' => '2022-04-21 12:00:53',
'ProductsPublication' => array(
[maximum depth reached]
)
),
(int) 10 => array(
'id' => '4227',
'name' => 'Epigenetic integrity of paternal imprints enhances the developmental
potential of androgenetic haploid embryonic stem cells.',
'authors' => 'Zhang, Hongling and Li, Yuanyuan and Ma, Yongjian and Lai,
Chongping and Yu, Qian and Shi, Guangyong and Li, Jinsong',
'description' => 'The use of two inhibitors of Mek1/2 and Gsk3β (2i) promotes the
generation of mouse diploid and haploid embryonic stem cells (ESCs) from
the inner cell mass of biparental and uniparental blastocysts,
respectively. However, a system enabling long-term maintenance of
imprints in ESCs has proven challenging. Here, we report that the use
of a two-step a2i (alternative two inhibitors of Src and Gsk3β,
TSa2i) derivation/culture protocol results in the establishment of
androgenetic haploid ESCs (AG-haESCs) with stable DNA methylation
at paternal DMRs (differentially DNA methylated regions) up to passage
60 that can efficiently support generating mice upon oocyte injection. We
also show coexistence of H3K9me3 marks and ZFP57 bindings with intact
DMR methylations. Furthermore, we demonstrate that TSa2i-treated
AG-haESCs are a heterogeneous cell population regarding paternal DMR
methylation. Strikingly, AG-haESCs with late passages display
increased paternal-DMR methylations and improved developmental potential
compared to early-passage cells, in part through the enhanced proliferation
of H19-DMR hypermethylated cells. Together, we establish
AG-haESCs that can long-term maintain paternal imprints.',
'date' => '2022-02-01',
'pmid' => 'https://doi.org/10.1007%2Fs13238-021-00890-3',
'doi' => '10.1007/s13238-021-00890-3',
'modified' => '2022-05-19 10:41:50',
'created' => '2022-05-19 10:41:50',
'ProductsPublication' => array(
[maximum depth reached]
)
),
(int) 11 => array(
'id' => '4367',
'name' => 'Cell-type specific transcriptional networks in root xylem adjacent celllayers',
'authors' => 'Asensi Fabado Maria Amparo et al.',
'description' => '<p>Transport of water, ions and signals from roots to leaves via the xylem vessels is essential for plant life and needs to be tightly regulated. The final composition of the transpiration stream before passage into the shoots is controlled by the xylem-adjacent cell layers, namely xylem parenchyma and pericycle, in the upper part of the root. To unravel regulatory networks in this strategically important location, we generated Arabidopsis lines expressing a nuclear tag under the control of the HKT1 promoter. HKT1 retrieves sodium from the xylem to prevent toxic levels in the shoot, and this function depends on its specific expression in upper root xylem-adjacent tissues. Based on FACS RNA-sequencing and INTACT ChIP-sequencing, we identified the gene repertoire that is preferentially expressed in the tagged cell types and discovered transcription factors experiencing cell-type specific loss of H3K27me3 demethylation. For one of these, ZAT6, we show that H3K27me3-demethylase REF6 is required for de-repression. Analysis of zat6 mutants revealed that ZAT6 activates a suite of cell-type specific downstream genes and restricts Na+ accumulation in the shoots. The combined Files open novel opportunities for ‘bottom-up’ causal dissection of cell-type specific regulatory networks that control root-to-shoot communication under environmental challenge.</p>',
'date' => '2022-02-01',
'pmid' => 'https://doi.org/10.1101%2F2022.02.04.479129',
'doi' => '10.1101/2022.02.04.479129',
'modified' => '2022-08-04 16:17:32',
'created' => '2022-08-04 14:55:36',
'ProductsPublication' => array(
[maximum depth reached]
)
),
(int) 12 => array(
'id' => '4326',
'name' => 'Loss of KMT2C reprograms the epigenomic landscape in hPSCsresulting in NODAL overexpression and a failure of hemogenic endotheliumspecification.',
'authors' => 'Maurya Shailendra et al.',
'description' => '<p>Germline or somatic variation in the family of KMT2 lysine methyltransferases have been associated with a variety of congenital disorders and cancers. Notably, -fusions are prevalent in 70\% of infant leukaemias but fail to phenocopy short latency leukaemogenesis in mammalian models, suggesting additional factors are necessary for transformation. Given the lack of additional somatic mutation, the role of epigenetic regulation in cell specification, and our prior results of germline variation in infant leukaemia patients, we hypothesized that germline dysfunction of KMT2C altered haematopoietic specification. In isogenic KO hPSCs, we found genome-wide differences in histone modifications at active and poised enhancers, leading to gene expression profiles akin to mesendoderm rather than mesoderm highlighted by a significant increase in NODAL expression and WNT inhibition, ultimately resulting in a lack of hemogenic endothelium specification. These unbiased multi-omic results provide new evidence for germline mechanisms increasing risk of early leukaemogenesis.</p>',
'date' => '2022-01-01',
'pmid' => 'https://doi.org/10.1080%2F15592294.2021.1954780',
'doi' => '10.1080/15592294.2021.1954780',
'modified' => '2022-06-20 09:27:45',
'created' => '2022-05-19 10:41:50',
'ProductsPublication' => array(
[maximum depth reached]
)
),
(int) 13 => array(
'id' => '4409',
'name' => 'Effects of GSK-J4 on JMJD3 Histone Demethylase in MouseProstate Cancer Xenografts.',
'authors' => 'Sanchez A. et al.',
'description' => '<p>BACKGROUND/AIM: Histone methylation status is required to control gene expression. H3K27me3 is an epigenetic tri-methylation modification to histone H3 controlled by the demethylase JMJD3. JMJD3 is dysregulated in a wide range of cancers and has been shown to control the expression of a specific growth-modulatory gene signature, making it an interesting candidate to better understand prostate tumor progression in vivo. This study aimed to identify the impact of JMJD3 inhibition by its inhibitor, GSK4, on prostate tumor growth in vivo. MATERIALS AND METHODS: Prostate cancer cell lines were implanted into Balb/c nude male mice. The effects of the selective JMJD3 inhibitor GSK-J4 on tumor growth were analyzed by bioluminescence assays and H3K27me3-regulated changes in gene expression were analyzed by ChIP-qPCR and RT-qPCR. RESULTS: JMJD3 inhibition contributed to an increase in tumor growth in androgen-independent (AR-) xenografts and a decrease in androgen-dependent (AR+). GSK-J4 treatment modulated H3K27me3 enrichment on the gene panel in DU-145-luc xenografts while it had little effect on PC3-luc and no effect on LNCaP-luc. Effects of JMJD3 inhibition affected the panel gene expression. CONCLUSION: JMJD3 has a differential effect in prostate tumor progression according to AR status. Our results suggest that JMJD3 is able to play a role independently of its demethylase function in androgen-independent prostate cancer. The effects of GSK-J4 on AR+ prostate xenografts led to a decrease in tumor growth.</p>',
'date' => '2022-01-01',
'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/35430567',
'doi' => '10.21873/cgp.20324',
'modified' => '2022-08-11 15:11:58',
'created' => '2022-08-11 12:14:50',
'ProductsPublication' => array(
[maximum depth reached]
)
),
(int) 14 => array(
'id' => '4540',
'name' => 'Chemokine switch regulated by TGF-β1 in cancer-associated fibroblastsubsets determines the efficacy of chemo-immunotherapy.',
'authors' => 'Vienot A. et al.',
'description' => '<p>Combining immunogenic cell death-inducing chemotherapies and PD-1 blockade can generate remarkable tumor responses. It is now well established that TGF-β1 signaling is a major component of treatment resistance and contributes to the cancer-related immunosuppressive microenvironment. However, whether TGF-β1 remains an obstacle to immune checkpoint inhibitor efficacy when immunotherapy is combined with chemotherapy is still to be determined. Several syngeneic murine models were used to investigate the role of TGF-β1 neutralization on the combinations of immunogenic chemotherapy (FOLFOX: 5-fluorouracil and oxaliplatin) and anti-PD-1. Cancer-associated fibroblasts (CAF) and immune cells were isolated from CT26 and PancOH7 tumor-bearing mice treated with FOLFOX, anti-PD-1 ± anti-TGF-β1 for bulk and single cell RNA sequencing and characterization. We showed that TGF-β1 neutralization promotes the therapeutic efficacy of FOLFOX and anti-PD-1 combination and induces the recruitment of antigen-specific CD8 T cells into the tumor. TGF-β1 neutralization is required in addition to chemo-immunotherapy to promote inflammatory CAF infiltration, a chemokine production switch in CAF leading to decreased CXCL14 and increased CXCL9/10 production and subsequent antigen-specific T cell recruitment. The immune-suppressive effect of TGF-β1 involves an epigenetic mechanism with chromatin remodeling of CXCL9 and CXCL10 promoters within CAF DNA in a G9a and EZH2-dependent fashion. Our results strengthen the role of TGF-β1 in the organization of a tumor microenvironment enriched in myofibroblasts where chromatin remodeling prevents CXCL9/10 production and limits the efficacy of chemo-immunotherapy.</p>',
'date' => '2022-01-01',
'pmid' => 'https://doi.org/10.1080%2F2162402x.2022.2144669',
'doi' => '10.1080/2162402X.2022.2144669',
'modified' => '2022-11-25 09:01:57',
'created' => '2022-11-24 08:49:52',
'ProductsPublication' => array(
[maximum depth reached]
)
),
(int) 15 => array(
'id' => '4283',
'name' => 'Coordination of EZH2 and SOX2 specifies human neural fate decision.',
'authors' => 'Zhao Yuan et al.',
'description' => '<p>Polycomb repressive complexes (PRCs) are essential in mouse gastrulation and specify neural ectoderm in human embryonic stem cells (hESCs), but the underlying molecular basis remains unclear. Here in this study, by employing an array of different approaches, such as gene knock-out, RNA-seq, ChIP-seq, et al., we uncover that EZH2, an important PRC factor, specifies the normal neural fate decision through repressing the competing meso/endoderm program. EZH2 hESCs show an aberrant re-activation of meso/endoderm genes during neural induction. At the molecular level, EZH2 represses meso/endoderm genes while SOX2 activates the neural genes to coordinately specify the normal neural fate. Moreover, EZH2 also supports the proliferation of human neural progenitor cells (NPCs) through repressing the aberrant expression of meso/endoderm program during culture. Together, our findings uncover the coordination of epigenetic regulators such as EZH2 and lineage factors like SOX2 in normal neural fate decision.</p>',
'date' => '2021-09-01',
'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/34487238',
'doi' => '10.1186/s13619-021-00092-6',
'modified' => '2022-05-23 10:10:34',
'created' => '2022-05-19 10:41:50',
'ProductsPublication' => array(
[maximum depth reached]
)
),
(int) 16 => array(
'id' => '4170',
'name' => 'A regulatory variant at 3q21.1 confers an increased pleiotropic risk forhyperglycemia and altered bone mineral density.',
'authors' => 'Sinnott-Armstrong, Nasa et al.',
'description' => '<p>Skeletal and glycemic traits have shared etiology, but the underlying genetic factors remain largely unknown. To identify genetic loci that may have pleiotropic effects, we studied Genome-wide association studies (GWASs) for bone mineral density and glycemic traits and identified a bivariate risk locus at 3q21. Using sequence and epigenetic modeling, we prioritized an adenylate cyclase 5 (ADCY5) intronic causal variant, rs56371916. This SNP changes the binding affinity of SREBP1 and leads to differential ADCY5 gene expression, altering the chromatin landscape from poised to repressed. These alterations result in bone- and type 2 diabetes-relevant cell-autonomous changes in lipid metabolism in osteoblasts and adipocytes. We validated our findings by directly manipulating the regulator SREBP1, the target gene ADCY5, and the variant rs56371916, which together imply a novel link between fatty acid oxidation and osteoblast differentiation. Our work, by systematic functional dissection of pleiotropic GWAS loci, represents a framework to uncover biological mechanisms affecting pleiotropic traits.</p>',
'date' => '2021-03-01',
'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33513366',
'doi' => '10.1016/j.cmet.2021.01.001',
'modified' => '2021-12-21 15:55:36',
'created' => '2021-12-06 15:53:19',
'ProductsPublication' => array(
[maximum depth reached]
)
),
(int) 17 => array(
'id' => '4196',
'name' => 'Functional annotations of three domestic animal genomes provide vitalresources for comparative and agricultural research.',
'authors' => 'Kern C. et al.',
'description' => '<p>Gene regulatory elements are central drivers of phenotypic variation and thus of critical importance towards understanding the genetics of complex traits. The Functional Annotation of Animal Genomes consortium was formed to collaboratively annotate the functional elements in animal genomes, starting with domesticated animals. Here we present an expansive collection of datasets from eight diverse tissues in three important agricultural species: chicken (Gallus gallus), pig (Sus scrofa), and cattle (Bos taurus). Comparative analysis of these datasets and those from the human and mouse Encyclopedia of DNA Elements projects reveal that a core set of regulatory elements are functionally conserved independent of divergence between species, and that tissue-specific transcription factor occupancy at regulatory elements and their predicted target genes are also conserved. These datasets represent a unique opportunity for the emerging field of comparative epigenomics, as well as the agricultural research community, including species that are globally important food resources.</p>',
'date' => '2021-03-01',
'pmid' => 'https://doi.org/10.1038%2Fs41467-021-22100-8',
'doi' => '10.1038/s41467-021-22100-8',
'modified' => '2022-01-06 14:30:41',
'created' => '2021-12-06 15:53:19',
'ProductsPublication' => array(
[maximum depth reached]
)
),
(int) 18 => array(
'id' => '4127',
'name' => 'The histone modification H3K4me3 is altered at the locus in Alzheimer'sdisease brain.',
'authors' => 'Smith, Adam et al.',
'description' => '<p>Several epigenome-wide association studies of DNA methylation have highlighted altered DNA methylation in the gene in Alzheimer's disease (AD) brain samples. However, no study has specifically examined histone modifications in the disease. We use chromatin immunoprecipitation-qPCR to quantify tri-methylation at histone 3 lysine 4 (H3K4me3) and 27 (H3K27me3) in the gene in entorhinal cortex from donors with high (n = 59) or low (n = 29) Alzheimer's disease pathology. We demonstrate decreased levels of H3K4me3, a marker of active gene transcription, with no change in H3K27me3, a marker of inactive genes. H3K4me3 is negatively correlated with DNA methylation in specific regions of the gene. Our study suggests that the gene shows altered epigenetic marks indicative of reduced gene activation in Alzheimer's disease.</p>',
'date' => '2021-02-01',
'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33815817',
'doi' => '10.2144/fsoa-2020-0161',
'modified' => '2021-12-07 10:16:08',
'created' => '2021-12-06 15:53:19',
'ProductsPublication' => array(
[maximum depth reached]
)
),
(int) 19 => array(
'id' => '4168',
'name' => 'The Essential Function of SETDB1 in Homologous Chromosome Pairing andSynapsis during Meiosis.',
'authors' => 'Cheng, Ee-Chun et al.',
'description' => '<p>SETDB1 is a histone-lysine N-methyltransferase critical for germline development. However, its function in early meiotic prophase I remains unknown. Here, we report that Setdb1 null spermatocytes display aberrant centromere clustering during leptotene, bouquet formation during zygotene, and subsequent failure in pairing and synapsis of homologous chromosomes, as well as compromised meiotic silencing of unsynapsed chromatin, which leads to meiotic arrest before pachytene and apoptosis of spermatocytes. H3K9me3 is enriched in centromeric or pericentromeric regions and is present in many sites throughout the genome, with a subset changed in the Setdb1 mutant. These observations indicate that SETDB1-mediated H3K9me3 is essential for the bivalent formation in early meiosis. Transcriptome analysis reveals the function of SETDB1 in repressing transposons and transposon-proximal genes and in regulating meiotic and somatic lineage genes. These findings highlight a mechanism in which SETDB1-mediated H3K9me3 during early meiosis ensures the formation of homologous bivalents and survival of spermatocytes.</p>',
'date' => '2021-01-01',
'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33406415',
'doi' => '10.1016/j.celrep.2020.108575',
'modified' => '2021-12-21 15:48:52',
'created' => '2021-12-06 15:53:19',
'ProductsPublication' => array(
[maximum depth reached]
)
),
(int) 20 => array(
'id' => '4323',
'name' => 'The tropical coral displays an unusual chromatin structure and showshistone H3 clipping plasticity upon bleaching.',
'authors' => 'Roquis D. et al. ',
'description' => '<p>is a hermatypic coral with strong ecological importance. Anthropogenic disturbances and global warming are major threats that can induce coral bleaching, the disruption of the mutualistic symbiosis between the coral host and its endosymbiotic algae. Previous works have shown that somaclonal colonies display different levels of survival depending on the environmental conditions they previously faced. Epigenetic mechanisms are good candidates to explain this phenomenon. However, almost no work had been published on the epigenome, especially on histone modifications. In this study, we aim at providing the first insight into chromatin structure of this species. We aligned the amino acid sequence of core histones with histone sequences from various phyla. We developed a centri-filtration on sucrose gradient to separate chromatin from the host and the symbiont. The presence of histone H3 protein and specific histone modifications were then detected by western blot performed on histone extraction done from bleached and healthy corals. Finally, micrococcal nuclease (MNase) digestions were undertaken to study nucleosomal organization. The centri-filtration enabled coral chromatin isolation with less than 2\% of contamination by endosymbiont material. Histone sequences alignments with other species show that displays on average ~90\% of sequence similarities with mice and ~96\% with other corals. H3 detection by western blot showed that H3 is clipped in healthy corals while it appeared to be intact in bleached corals. MNase treatment failed to provide the usual mononucleosomal digestion, a feature shared with some cnidarian, but not all; suggesting an unusual chromatin structure. These results provide a first insight into the chromatin, nucleosome and histone structure of . The unusual patterns highlighted in this study and partly shared with other cnidarian will need to be further studied to better understand its role in corals.</p>',
'date' => '2021-01-01',
'pmid' => 'https://doi.org/10.12688%2Fwellcomeopenres.17058.1',
'doi' => '10.12688/wellcomeopenres.17058.2',
'modified' => '2022-08-02 17:04:56',
'created' => '2022-05-19 10:41:50',
'ProductsPublication' => array(
[maximum depth reached]
)
),
(int) 21 => array(
'id' => '4207',
'name' => 'EZH2 and KDM6B Expressions Are Associated with Specific EpigeneticSignatures during EMT in Non Small Cell Lung Carcinomas.',
'authors' => 'Lachat C. et al. ',
'description' => '<p>The role of Epigenetics in Epithelial Mesenchymal Transition (EMT) has recently emerged. Two epigenetic enzymes with paradoxical roles have previously been associated to EMT, EZH2 (Enhancer of Zeste 2 Polycomb Repressive Complex 2 (PRC2) Subunit), a lysine methyltranserase able to add the H3K27me3 mark, and the histone demethylase KDM6B (Lysine Demethylase 6B), which can remove the H3K27me3 mark. Nevertheless, it still remains unclear how these enzymes, with apparent opposite activities, could both promote EMT. In this study, we evaluated the function of these two enzymes using an EMT-inducible model, the lung cancer A549 cell line. ChIP-seq coupled with transcriptomic analysis showed that EZH2 and KDM6B were able to target and modulate the expression of different genes during EMT. Based on this analysis, we described INHBB, WTN5B, and ADAMTS6 as new EMT markers regulated by epigenetic modifications and directly implicated in EMT induction.</p>',
'date' => '2020-12-01',
'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33291363',
'doi' => '10.3390/cancers12123649',
'modified' => '2022-01-13 14:50:18',
'created' => '2021-12-06 15:53:19',
'ProductsPublication' => array(
[maximum depth reached]
)
),
(int) 22 => array(
'id' => '4071',
'name' => 'A histone H3.3K36M mutation in mice causes an imbalance of histonemodifications and defects in chondrocyte differentiation.',
'authors' => 'Abe, Shusaku and Nagatomo, Hiroaki and Sasaki, Hiroyuki and Ishiuchi,Takashi',
'description' => '<p>Histone lysine-to-methionine (K-to-M) mutations have been identified as driver mutations in human cancers. Interestingly, these 'oncohistone' mutations inhibit the activity of histone methyltransferases. Therefore, they can potentially be used as versatile tools to investigate the roles of histone modifications. In this study, we generated a genetically engineered mouse line in which an H3.3K36M mutation could be induced in the endogenous gene. Since H3.3K36M has been identified as a causative mutation of human chondroblastoma, we induced this mutation in the chondrocyte lineage in mouse embryonic limbs. We found that H3.3K36M causes a global reduction in H3K36me2 and defects in chondrocyte differentiation. Importantly, the reduction of H3K36me2 was accompanied by a collapse of normal H3K27me3 distribution. Furthermore, the changes in H3K27me3, especially the loss of H3K27me3 at gene regulatory elements, were associated with the mis-regulated expression of a set of genes important for limb development, including HoxA cluster genes. Thus, through the induction of the H3.3K36M mutation, we reveal the importance of maintaining the balance between H3K36me2 and H3K27me3 during chondrocyte differentiation and limb development.</p>',
'date' => '2020-11-01',
'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33135541',
'doi' => '10.1080/15592294.2020.1841873',
'modified' => '2021-02-19 17:58:57',
'created' => '2021-02-18 10:21:53',
'ProductsPublication' => array(
[maximum depth reached]
)
),
(int) 23 => array(
'id' => '4210',
'name' => 'Trans- and cis-acting effects of Firre on epigenetic features of theinactive X chromosome.',
'authors' => 'Fang, He and Bonora, Giancarlo and Lewandowski, Jordan P and Thakur,Jitendra and Filippova, Galina N and Henikoff, Steven and Shendure, Jay andDuan, Zhijun and Rinn, John L and Deng, Xinxian and Noble, William S andDisteche, Christine M',
'description' => '<p>Firre encodes a lncRNA involved in nuclear organization. Here, we show that Firre RNA expressed from the active X chromosome maintains histone H3K27me3 enrichment on the inactive X chromosome (Xi) in somatic cells. This trans-acting effect involves SUZ12, reflecting interactions between Firre RNA and components of the Polycomb repressive complexes. Without Firre RNA, H3K27me3 decreases on the Xi and the Xi-perinucleolar location is disrupted, possibly due to decreased CTCF binding on the Xi. We also observe widespread gene dysregulation, but not on the Xi. These effects are measurably rescued by ectopic expression of mouse or human Firre/FIRRE transgenes, supporting conserved trans-acting roles. We also find that the compact 3D structure of the Xi partly depends on the Firre locus and its RNA. In common lymphoid progenitors and T-cells Firre exerts a cis-acting effect on maintenance of H3K27me3 in a 26 Mb region around the locus, demonstrating cell type-specific trans- and cis-acting roles of this lncRNA.</p>',
'date' => '2020-11-01',
'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/33247132',
'doi' => '10.1038/s41467-020-19879-3',
'modified' => '2022-01-13 15:03:45',
'created' => '2021-12-06 15:53:19',
'ProductsPublication' => array(
[maximum depth reached]
)
),
(int) 24 => array(
'id' => '4073',
'name' => 'NSD1-deposited H3K36me2 directs de novo methylation in the mouse malegermline and counteracts Polycomb-associated silencing.',
'authors' => 'Shirane, Kenjiro and Miura, Fumihito and Ito, Takashi and Lorincz, MatthewC',
'description' => '<p>De novo DNA methylation (DNAme) in mammalian germ cells is dependent on DNMT3A and DNMT3L. However, oocytes and spermatozoa show distinct patterns of DNAme. In mouse oocytes, de novo DNAme requires the lysine methyltransferase (KMTase) SETD2, which deposits H3K36me3. We show here that SETD2 is dispensable for de novo DNAme in the male germline. Instead, the lysine methyltransferase NSD1, which broadly deposits H3K36me2 in euchromatic regions, plays a critical role in de novo DNAme in prospermatogonia, including at imprinted genes. However, males deficient in germline NSD1 show a more severe defect in spermatogenesis than Dnmt3l males. Notably, unlike DNMT3L, NSD1 safeguards a subset of genes against H3K27me3-associated transcriptional silencing. In contrast, H3K36me2 in oocytes is predominantly dependent on SETD2 and coincides with H3K36me3. Furthermore, females with NSD1-deficient oocytes are fertile. Thus, the sexually dimorphic pattern of DNAme in mature mouse gametes is orchestrated by distinct profiles of H3K36 methylation.</p>',
'date' => '2020-10-01',
'pmid' => 'https://www.ncbi.nlm.nih.gov/pubmed/32929285',
'doi' => '10.1038/s41588-020-0689-z',
'modified' => '2021-02-19 18:02:40',
'created' => '2021-02-18 10:21:53',
'ProductsPublication' => array(
[maximum depth reached]
)
),
(int) 25 => array(
'id' => '4004',
'name' => 'Distinct and temporary-restricted epigenetic mechanisms regulate human αβ and γδ T cell development ',
'authors' => 'Roels J, Kuchmiy A, De Decker M, et al. ',
'description' => '<p>The development of TCRαβ and TCRγδ T cells comprises a step-wise process in which regulatory events control differentiation and lineage outcome. To clarify these mechanisms, we employed RNA-sequencing, ATAC-sequencing and ChIPmentation on well-defined thymocyte subsets that represent the continuum of human T cell development. The chromatin accessibility dynamics show clear stage specificity and reveal that human T cell-lineage commitment is marked by GATA3- and BCL11B-dependent closing of PU.1 sites. A temporary increase in H3K27me3 without open chromatin modifications is unique for β-selection, whereas emerging γδ T cells, which originate from common precursors of β-selected cells, show large chromatin accessibility changes due to strong T cell receptor (TCR) signaling. Furthermore, we unravel distinct chromatin landscapes between CD4<sup>+</sup> and CD8<sup>+</sup> αβ-lineage cells that support their effector functions and reveal gene-specific mechanisms that define mature T cells. This resource provides a framework for studying gene regulatory mechanisms that drive normal and malignant human T cell development.</p>',
'date' => '2020-07-27',
'pmid' => 'https://pubmed.ncbi.nlm.nih.gov/32719521/',
'doi' => ' 10.1038/s41590-020-0747-9 ',
'modified' => '2021-01-29 14:12:02',
'created' => '2020-09-11 15:17:58',
'ProductsPublication' => array(
[maximum depth reached]
)
),
(int) 26 => array(
'id' => '4032',
'name' => 'MeCP2 regulates gene expression through recognition of H3K27me3.',
'authors' => 'Lee, W and Kim, J and Yun, JM and Ohn, T and Gong, Q',
'description' => '<p>MeCP2 plays a multifaceted role in gene expression regulation and chromatin organization. Interaction between MeCP2 and methylated DNA in the regulation of gene expression is well established. However, the widespread distribution of MeCP2 suggests it has additional interactions with chromatin. Here we demonstrate, by both biochemical and genomic analyses, that MeCP2 directly interacts with nucleosomes and its genomic distribution correlates with that of H3K27me3. In particular, the methyl-CpG-binding domain of MeCP2 shows preferential interactions with H3K27me3. We further observe that the impact of MeCP2 on transcriptional changes correlates with histone post-translational modification patterns. Our findings indicate that MeCP2 interacts with genomic loci via binding to DNA as well as histones, and that interaction between MeCP2 and histone proteins plays a key role in gene expression regulation.</p>',
'date' => '2020-07-19',
'pmid' => 'http://www.pubmed.gov/32561780',
'doi' => '10.1038/s41467-020-16907-0',
'modified' => '2020-12-16 18:05:17',
'created' => '2020-10-12 14:54:59',
'ProductsPublication' => array(
[maximum depth reached]
)
),
(int) 27 => array(
'id' => '3926',
'name' => 'TET-Mediated Hypermethylation Primes SDH-Deficient Cells for HIF2α-Driven Mesenchymal Transition.',
'authors' => 'Morin A, Goncalves J, Moog S, Castro-Vega LJ, Job S, Buffet A, Fontenille MJ, Woszczyk J, Gimenez-Roqueplo AP, Letouzé E, Favier J',
'description' => '<p>Loss-of-function mutations in the SDHB subunit of succinate dehydrogenase predispose patients to aggressive tumors characterized by pseudohypoxic and hypermethylator phenotypes. The mechanisms leading to DNA hypermethylation and its contribution to SDH-deficient cancers remain undemonstrated. We examine the genome-wide distribution of 5-methylcytosine and 5-hydroxymethylcytosine and their correlation with RNA expression in SDHB-deficient tumors and murine Sdhb cells. We report that DNA hypermethylation results from TET inhibition. Although it preferentially affects PRC2 targets and known developmental genes, PRC2 activity does not contribute to the DNA hypermethylator phenotype. We also prove, in vitro and in vivo, that TET silencing, although recapitulating the methylation profile of Sdhb cells, is not sufficient to drive their EMT-like phenotype, which requires additional HIF2α activation. Altogether, our findings reveal synergistic roles of TET repression and pseudohypoxia in the acquisition of metastatic traits, providing a rationale for targeting HIF2α and DNA methylation in SDH-associated malignancies.</p>',
'date' => '2020-03-31',
'pmid' => 'http://www.pubmed.gov/32234487',
'doi' => '10.1016/j.celrep.2020.03.022',
'modified' => '2020-08-17 10:50:11',
'created' => '2020-08-10 12:12:25',
'ProductsPublication' => array(
[maximum depth reached]
)
),
(int) 28 => array(
'id' => '3924',
'name' => 'Alu retrotransposons modulate Nanog expression through dynamic changes in regional chromatin conformation via aryl hydrocarbon receptor.',
'authors' => 'González-Rico FJ, Vicente-García C, Fernández A, Muñoz-Santos D, Montoliu L, Morales-Hernández A, Merino JM, Román AC, Fernández-Salguero PM',
'description' => '<p>Transcriptional repression of Nanog is an important hallmark of stem cell differentiation. Chromatin modifications have been linked to the epigenetic profile of the Nanog gene, but whether chromatin organization actually plays a causal role in Nanog regulation is still unclear. Here, we report that the formation of a chromatin loop in the Nanog locus is concomitant to its transcriptional downregulation during human NTERA-2 cell differentiation. We found that two Alu elements flanking the Nanog gene were bound by the aryl hydrocarbon receptor (AhR) and the insulator protein CTCF during cell differentiation. Such binding altered the profile of repressive histone modifications near Nanog likely leading to gene insulation through the formation of a chromatin loop between the two Alu elements. Using a dCAS9-guided proteomic screening, we found that interaction of the histone methyltransferase PRMT1 and the chromatin assembly factor CHAF1B with the Alu elements flanking Nanog was required for chromatin loop formation and Nanog repression. Therefore, our results uncover a chromatin-driven, retrotransposon-regulated mechanism for the control of Nanog expression during cell differentiation.</p>',
'date' => '2020-03-14',
'pmid' => 'http://www.pubmed.gov/32169107',
'doi' => '10.1186/s13072‑020‑00336‑w',
'modified' => '2020-08-17 10:52:25',
'created' => '2020-08-10 12:12:25',
'ProductsPublication' => array(
[maximum depth reached]
)
),
(int) 29 => array(
'id' => '3873',
'name' => 'Inhibition of methyltransferase activity of enhancer of zeste 2 leads to enhanced lipid accumulation and altered chromatin status in zebrafish.',
'authors' => 'den Broeder MJ, Ballangby J, Kamminga LM, Aleström P, Legler J, Lindeman LC, Kamstra JH',
'description' => '<p>BACKGROUND: Recent studies indicate that exposure to environmental chemicals may increase susceptibility to developing metabolic diseases. This susceptibility may in part be caused by changes to the epigenetic landscape which consequently affect gene expression and lead to changes in lipid metabolism. The epigenetic modifier enhancer of zeste 2 (Ezh2) is a histone H3K27 methyltransferase implicated to play a role in lipid metabolism and adipogenesis. In this study, we used the zebrafish (Danio rerio) to investigate the role of Ezh2 on lipid metabolism and chromatin status following developmental exposure to the Ezh1/2 inhibitor PF-06726304 acetate. We used the environmental chemical tributyltin (TBT) as a positive control, as this chemical is known to act on lipid metabolism via EZH-mediated pathways in mammals. RESULTS: Zebrafish embryos (0-5 days post-fertilization, dpf) exposed to non-toxic concentrations of PF-06726304 acetate (5 μM) and TBT (1 nM) exhibited increased lipid accumulation. Changes in chromatin were analyzed by the assay for transposase-accessible chromatin sequencing (ATAC-seq) at 50% epiboly (5.5 hpf). We observed 349 altered chromatin regions, predominantly located at H3K27me3 loci and mostly more open chromatin in the exposed samples. Genes associated to these loci were linked to metabolic pathways. In addition, a selection of genes involved in lipid homeostasis, adipogenesis and genes specifically targeted by PF-06726304 acetate via altered chromatin accessibility were differentially expressed after TBT and PF-06726304 acetate exposure at 5 dpf, but not at 50% epiboly stage. One gene, cebpa, did not show a change in chromatin, but did show a change in gene expression at 5 dpf. Interestingly, underlying H3K27me3 marks were significantly decreased at this locus at 50% epiboly. CONCLUSIONS: Here, we show for the first time the applicability of ATAC-seq as a tool to investigate toxicological responses in zebrafish. Our analysis indicates that Ezh2 inhibition leads to a partial primed state of chromatin linked to metabolic pathways which results in gene expression changes later in development, leading to enhanced lipid accumulation. Although ATAC-seq seems promising, our in-depth assessment of the cebpa locus indicates that we need to consider underlying epigenetic marks as well.</p>',
'date' => '2020-02-12',
'pmid' => 'http://www.pubmed.gov/32051014',
'doi' => '10.1186/s13072-020-0329-y',
'modified' => '2020-03-20 17:42:02',
'created' => '2020-03-13 13:45:54',
'ProductsPublication' => array(
[maximum depth reached]
)
),
(int) 30 => array(
'id' => '3856',
'name' => 'Polycomb Group Proteins Regulate Chromatin Architecture in Mouse Oocytes and Early Embryos.',
'authors' => 'Du Z, Zheng H, Kawamura YK, Zhang K, Gassler J, Powell S, Xu Q, Lin Z, Xu K, Zhou Q, Ozonov EA, Véron N, Huang B, Li L, Yu G, Liu L, Au Yeung WK, Wang P, Chang L, Wang Q, He A, Sun Y, Na J, Sun Q, Sasaki H, Tachibana K, Peters AHFM, Xie W',
'description' => '<p>In mammals, chromatin organization undergoes drastic reorganization during oocyte development. However, the dynamics of three-dimensional chromatin structure in this process is poorly characterized. Using low-input Hi-C (genome-wide chromatin conformation capture), we found that a unique chromatin organization gradually appears during mouse oocyte growth. Oocytes at late stages show self-interacting, cohesin-independent compartmental domains marked by H3K27me3, therefore termed Polycomb-associating domains (PADs). PADs and inter-PAD (iPAD) regions form compartment-like structures with strong inter-domain interactions among nearby PADs. PADs disassemble upon meiotic resumption from diplotene arrest but briefly reappear on the maternal genome after fertilization. Upon maternal depletion of Eed, PADs are largely intact in oocytes, but their reestablishment after fertilization is compromised. By contrast, depletion of Polycomb repressive complex 1 (PRC1) proteins attenuates PADs in oocytes, which is associated with substantial gene de-repression in PADs. These data reveal a critical role of Polycomb in regulating chromatin architecture during mammalian oocyte growth and early development.</p>',
'date' => '2020-02-04',
'pmid' => 'http://www.pubmed.gov/31837995',
'doi' => '10.1016/j.molcel.2019.11.011',
'modified' => '2020-03-20 17:58:29',
'created' => '2020-03-13 13:45:54',
'ProductsPublication' => array(
[maximum depth reached]
)
),
(int) 31 => array(
'id' => '3840',
'name' => 'Allelic H3K27me3 to allelic DNA methylation switch maintains noncanonical imprinting in extraembryonic cells',
'authors' => 'Chen Zhiyuan, Yin Qiangzong, Inoue Azusa, Zhang Chunxia, Zhang Yi',
'description' => '<p>Faithful maintenance of genomic imprinting is essential for mammalian development. While germline DNA methylation–dependent (canonical) imprinting is relatively stable during development, the recently found oocyte-derived H3K27me3-mediated noncanonical imprinting is mostly transient in early embryos, with some genes important for placental development maintaining imprinted expression in the extraembryonic lineage. How these noncanonical imprinted genes maintain their extraembryonic-specific imprinting is unknown. Here, we report that maintenance of noncanonical imprinting requires maternal allele–specific de novo DNA methylation [i.e., somatic differentially methylated regions (DMRs)] at implantation. The somatic DMRs are located at the gene promoters, with paternal allele–specific H3K4me3 established during preimplantation development. Genetic manipulation revealed that both maternal EED and zygotic DNMT3A/3B are required for establishing somatic DMRs and maintaining noncanonical imprinting. Thus, our study not only reveals the mechanism underlying noncanonical imprinting maintenance but also sheds light on how histone modifications in oocytes may shape somatic DMRs in postimplantation embryos.</p>',
'date' => '2019-12-20',
'pmid' => 'https://advances.sciencemag.org/content/5/12/eaay7246',
'doi' => '10.1126/sciadv.aay7246',
'modified' => '2020-02-20 11:16:43',
'created' => '2020-02-13 10:02:44',
'ProductsPublication' => array(
[maximum depth reached]
)
),
(int) 32 => array(
'id' => '3841',
'name' => 'Inhibition of Histone Demethylases LSD1 and UTX Regulates ERα Signaling in Breast Cancer.',
'authors' => 'Benedetti R, Dell'Aversana C, De Marchi T, Rotili D, Liu NQ, Novakovic B, Boccella S, Di Maro S, Cosconati S, Baldi A, Niméus E, Schultz J, Höglund U, Maione S, Papulino C, Chianese U, Iovino F, Federico A, Mai A, Stunnenberg HG, Nebbioso A, Altucci L',
'description' => '<p>In breast cancer, Lysine-specific demethylase-1 (LSD1) and other lysine demethylases (KDMs), such as Lysine-specific demethylase 6A also known as Ubiquitously transcribed tetratricopeptide repeat, X chromosome (UTX), are co-expressed and co-localize with estrogen receptors (ERs), suggesting the potential use of hybrid (epi)molecules to target histone methylation and therefore regulate/redirect hormone receptor signaling. Here, we report on the biological activity of a dual-KDM inhibitor (MC3324), obtained by coupling the chemical properties of tranylcypromine, a known LSD1 inhibitor, with the 2OG competitive moiety developed for JmjC inhibition. MC3324 displays unique features not exhibited by the single moieties and well-characterized mono-pharmacological inhibitors. Inhibiting LSD1 and UTX, MC3324 induces significant growth arrest and apoptosis in hormone-responsive breast cancer model accompanied by a robust increase in H3K4me2 and H3K27me3. MC3324 down-regulates ERα in breast cancer at both transcriptional and non-transcriptional levels, mimicking the action of a selective endocrine receptor disruptor. MC3324 alters the histone methylation of ERα-regulated promoters, thereby affecting the transcription of genes involved in cell surveillance, hormone response, and death. MC3324 reduces cell proliferation in ex vivo breast cancers, as well as in breast models with acquired resistance to endocrine therapies. Similarly, MC3324 displays tumor-selective potential in vivo, in both xenograft mice and chicken embryo models, with no toxicity and good oral efficacy. This epigenetic multi-target approach is effective and may overcome potential mechanism(s) of resistance in breast cancer.</p>',
'date' => '2019-12-16',
'pmid' => 'http://www.pubmed.gov/31888209',
'doi' => '10.3390/cancers11122027',
'modified' => '2020-02-20 11:15:48',
'created' => '2020-02-13 10:02:44',
'ProductsPublication' => array(
[maximum depth reached]
)
),
(int) 33 => array(
'id' => '3762',
'name' => 'Transit amplifying cells coordinate mouse incisor mesenchymal stem cell activation.',
'authors' => 'Walker JV, Zhuang H, Singer D, Illsley CS, Kok WL, Sivaraj KK, Gao Y, Bolton C, Liu Y, Zhao M, Grayson PRC, Wang S, Karbanová J, Lee T, Ardu S, Lai Q, Liu J, Kassem M, Chen S, Yang K, Bai Y, Tredwin C, Zambon AC, Corbeil D, Adams R, Abdallah BM, Hu B',
'description' => '<p>Stem cells (SCs) receive inductive cues from the surrounding microenvironment and cells. Limited molecular evidence has connected tissue-specific mesenchymal stem cells (MSCs) with mesenchymal transit amplifying cells (MTACs). Using mouse incisor as the model, we discover a population of MSCs neibouring to the MTACs and epithelial SCs. With Notch signaling as the key regulator, we disclose molecular proof and lineage tracing evidence showing the distinct MSCs contribute to incisor MTACs and the other mesenchymal cell lineages. MTACs can feedback and regulate the homeostasis and activation of CL-MSCs through Delta-like 1 homolog (Dlk1), which balances MSCs-MTACs number and the lineage differentiation. Dlk1's function on SCs priming and self-renewal depends on its biological forms and its gene expression is under dynamic epigenetic control. Our findings can be validated in clinical samples and applied to accelerate tooth wound healing, providing an intriguing insight of how to direct SCs towards tissue regeneration.</p>',
'date' => '2019-08-09',
'pmid' => 'http://www.pubmed.gov/31399601',
'doi' => '10.1038/s41467-019-11611-0',
'modified' => '2019-10-03 10:03:31',
'created' => '2019-10-02 16:16:55',
'ProductsPublication' => array(
[maximum depth reached]
)
),
(int) 34 => array(
'id' => '3718',
'name' => 'The Toxoplasma effector TEEGR promotes parasite persistence by modulating NF-κB signalling via EZH2.',
'authors' => 'Braun L, Brenier-Pinchart MP, Hammoudi PM, Cannella D, Kieffer-Jaquinod S, Vollaire J, Josserand V, Touquet B, Couté Y, Tardieux I, Bougdour A, Hakimi MA',
'description' => '<p>The protozoan parasite Toxoplasma gondii has co-evolved with its homeothermic hosts (humans included) strategies that drive its quasi-asymptomatic persistence in hosts, hence optimizing the chance of transmission to new hosts. Persistence, which starts with a small subset of parasites that escape host immune killing and colonize the so-called immune privileged tissues where they differentiate into a low replicating stage, is driven by the interleukin 12 (IL-12)-interferon-γ (IFN-γ) axis. Recent characterization of a family of Toxoplasma effectors that are delivered into the host cell, in which they rewire the host cell gene expression, has allowed the identification of regulators of the IL-12-IFN-γ axis, including repressors. We now report on the dense granule-resident effector, called TEEGR (Toxoplasma E2F4-associated EZH2-inducing gene regulator) that counteracts the nuclear factor-κB (NF-κB) signalling pathway. Once exported into the host cell, TEEGR ends up in the nucleus where it not only complexes with the E2F3 and E2F4 host transcription factors to induce gene expression, but also promotes shaping of a non-permissive chromatin through its capacity to switch on EZH2. Remarkably, EZH2 fosters the epigenetic silencing of a subset of NF-κB-regulated cytokines, thereby strongly contributing to the host immune equilibrium that influences the host immune response and promotes parasite persistence in mice.</p>',
'date' => '2019-07-01',
'pmid' => 'http://www.pubmed.gov/31036909',
'doi' => '10.1038/s41564-019-0431-8',
'modified' => '2019-07-04 18:09:37',
'created' => '2019-07-04 10:42:34',
'ProductsPublication' => array(
[maximum depth reached]
)
),
(int) 35 => array(
'id' => '3732',
'name' => 'Kdm6b regulates context-dependent hematopoietic stem cell self-renewal and leukemogenesis.',
'authors' => 'Mallaney C, Ostrander EL, Celik H, Kramer AC, Martens A, Kothari A, Koh WK, Haussler E, Iwamori N, Gontarz P, Zhang B, Challen GA',
'description' => '<p>The histone demethylase KDM6B (JMJD3) is upregulated in blood disorders, suggesting that it may have important pathogenic functions. Here we examined the function of Kdm6b in hematopoietic stem cells (HSC) to evaluate its potential as a therapeutic target. Loss of Kdm6b lead to depletion of phenotypic and functional HSCs in adult mice, and Kdm6b is necessary for HSC self-renewal in response to inflammatory and proliferative stress. Loss of Kdm6b leads to a pro-differentiation poised state in HSCs due to the increased expression of the AP-1 transcription factor complex (Fos and Jun) and immediate early response (IER) genes. These gene expression changes occurred independently of chromatin modifications. Targeting AP-1 restored function of Kdm6b-deficient HSCs, suggesting that Kdm6b regulates this complex during HSC stress response. We also show Kdm6b supports developmental context-dependent leukemogenesis for T-cell acute lymphoblastic leukemia (T-ALL) and M5 acute myeloid leukemia (AML). Kdm6b is required for effective fetal-derived T-ALL and adult-derived AML, but not vice versa. These studies identify a crucial role for Kdm6b in regulating HSC self-renewal in different contexts, and highlight the potential of KDM6B as a therapeutic target in different hematopoietic malignancies.</p>',
'date' => '2019-04-01',
'pmid' => 'http://www.pubmed.gov/30936419',
'doi' => '10.1038/s41375-019-0462-4',
'modified' => '2019-08-07 09:14:05',
'created' => '2019-07-31 13:35:50',
'ProductsPublication' => array(
[maximum depth reached]
)
),
(int) 36 => array(
'id' => '3675',
'name' => 'H3K27me3 is an epigenetic barrier while KDM6A overexpression improves nuclear reprogramming efficiency.',
'authors' => 'Zhou C, Wang Y, Zhang J, Su J, An Q, Liu X, Zhang M, Wang Y, Liu J, Zhang Y',
'description' => '<p>Aberrant epigenetic reprogramming is a major factor of developmental failure of cloned embryos. Histone H3 lysine 27 trimethylation (H3K27me3), a histone mark for transcriptional repression, plays important roles in mammalian embryonic development and induced pluripotent stem cell (iPSC) generation. The global loss of H3K27me3 marks may facilitate iPSC generation in mice and humans. However, the H3K27me3 level and its role in bovine somatic cell nuclear transfer (SCNT) reprogramming remain poorly understood. Here, we show that SCNT embryos exhibit global H3K27me3 hypermethylation from the 2- to 8-cell stage and that its removal by ectopically expressed H3K27me3 lysine demethylase (KDM)6A greatly improves nuclear reprogramming efficiency. In contrast, H3K27me3 reduction by H3K27me3 methylase enhancer of zeste 2 polycomb repressive complex knockdown or donor cell treatment with the enhancer of zeste 2 polycomb repressive complex-selective inhibitor GSK343 suppressed blastocyst formation by SCNT embryos. KDM6A overexpression enhanced the transcription of genes involved in cell adhesion and cellular metabolism and X-linked genes. Furthermore, we identified methyl-CpG-binding domain protein 3-like 2, which was reactivated by KDM6A, as a factor that is required for effective reprogramming in bovines. These results show that H3K27me3 functions as an epigenetic barrier and that KDM6A overexpression improves SCNT efficiency by facilitating transcriptional reprogramming.-Zhou, C., Wang, Y., Zhang, J., Su, J., An, Q., Liu, X., Zhang, M., Wang, Y., Liu, J., Zhang, Y. H3K27me3 is an epigenetic barrier while KDM6A overexpression improves nuclear reprogramming efficiency.</p>',
'date' => '2019-03-01',
'pmid' => 'http://www.pubmed.gov/30673507',
'doi' => '10.1096/fj.201801887R',
'modified' => '2019-07-01 11:24:26',
'created' => '2019-06-21 14:55:31',
'ProductsPublication' => array(
[maximum depth reached]
)
),
(int) 37 => array(
'id' => '3629',
'name' => 'Comprehensive Analysis of Chromatin States in Atypical Teratoid/Rhabdoid Tumor Identifies Diverging Roles for SWI/SNF and Polycomb in Gene Regulation.',
'authors' => 'Erkek S, Johann PD, Finetti MA, Drosos Y, Chou HC, Zapatka M, Sturm D, Jones DTW, Korshunov A, Rhyzova M, Wolf S, Mallm JP, Beck K, Witt O, Kulozik AE, Frühwald MC, Northcott PA, Korbel JO, Lichter P, Eils R, Gajjar A, Roberts CWM, Williamson D, Hasselbla',
'description' => '<p>Biallelic inactivation of SMARCB1, encoding a member of the SWI/SNF chromatin remodeling complex, is the hallmark genetic aberration of atypical teratoid rhabdoid tumors (ATRT). Here, we report how loss of SMARCB1 affects the epigenome in these tumors. Using chromatin immunoprecipitation sequencing (ChIP-seq) on primary tumors for a series of active and repressive histone marks, we identified the chromatin states differentially represented in ATRTs compared with other brain tumors and non-neoplastic brain. Re-expression of SMARCB1 in ATRT cell lines enabled confirmation of our genome-wide findings for the chromatin states. Additional generation of ChIP-seq data for SWI/SNF and Polycomb group proteins and the transcriptional repressor protein REST determined differential dependencies of SWI/SNF and Polycomb complexes in regulation of diverse gene sets in ATRTs.</p>',
'date' => '2019-01-14',
'pmid' => 'http://www.pubmed.gov/30595504',
'doi' => '10.1016/j.ccell.2018.11.014',
'modified' => '2019-05-08 12:27:57',
'created' => '2019-04-25 11:11:44',
'ProductsPublication' => array(
[maximum depth reached]
)
),
(int) 38 => array(
'id' => '3686',
'name' => 'Gamma radiation induces locus specific changes to histone modification enrichment in zebrafish and Atlantic salmon.',
'authors' => 'Lindeman LC, Kamstra JH, Ballangby J, Hurem S, Martín LM, Brede DA, Teien HC, Oughton DH, Salbu B, Lyche JL, Aleström P',
'description' => '<p>Ionizing radiation is a recognized genotoxic agent, however, little is known about the role of the functional form of DNA in these processes. Post translational modifications on histone proteins control the organization of chromatin and hence control transcriptional responses that ultimately affect the phenotype. The purpose of this study was to investigate effects on chromatin caused by ionizing radiation in fish. Direct exposure of zebrafish (Danio rerio) embryos to gamma radiation (10.9 mGy/h for 3h) induced hyper-enrichment of H3K4me3 at the genes hnf4a, gmnn and vegfab. A similar relative hyper-enrichment was seen at the hnf4a loci of irradiated Atlantic salmon (Salmo salar) embryos (30 mGy/h for 10 days). At the selected genes in ovaries of adult zebrafish irradiated during gametogenesis (8.7 and 53 mGy/h for 27 days), a reduced enrichment of H3K4me3 was observed, which was correlated with reduced levels of histone H3 was observed. F1 embryos of the exposed parents showed hyper-methylation of H3K4me3, H3K9me3 and H3K27me3 on the same three loci, while these differences were almost negligible in F2 embryos. Our results from three selected loci suggest that ionizing radiation can affect chromatin structure and organization, and that these changes can be detected in F1 offspring, but not in subsequent generations.</p>',
'date' => '2019-01-01',
'pmid' => 'http://www.pubmed.gov/30759148',
'doi' => '10.1371/journal.pone.0212123',
'modified' => '2019-06-28 13:57:39',
'created' => '2019-06-21 14:55:31',
'ProductsPublication' => array(
[maximum depth reached]
)
),
(int) 39 => array(
'id' => '3607',
'name' => 'Mutant p63 Affects Epidermal Cell Identity through Rewiring the Enhancer Landscape.',
'authors' => 'Qu J, Tanis SEJ, Smits JPH, Kouwenhoven EN, Oti M, van den Bogaard EH, Logie C, Stunnenberg HG, van Bokhoven H, Mulder KW, Zhou H',
'description' => '<p>Transcription factor p63 is a key regulator of epidermal keratinocyte proliferation and differentiation. Mutations in the p63 DNA-binding domain are associated with ectrodactyly, ectodermal dysplasia, and cleft lip/palate (EEC) syndrome. However, the underlying molecular mechanism of these mutations remains unclear. Here, we characterized the transcriptome and epigenome of p63 mutant keratinocytes derived from EEC patients. The transcriptome of p63 mutant keratinocytes deviated from the normal epidermal cell identity. Epigenomic analyses showed an altered enhancer landscape in p63 mutant keratinocytes contributed by loss of p63-bound active enhancers and unexpected gain of enhancers. The gained enhancers were frequently bound by deregulated transcription factors such as RUNX1. Reversing RUNX1 overexpression partially rescued deregulated gene expression and the altered enhancer landscape. Our findings identify a disease mechanism whereby mutant p63 rewires the enhancer landscape and affects epidermal cell identity, consolidating the pivotal role of p63 in controlling the enhancer landscape of epidermal keratinocytes.</p>',
'date' => '2018-12-18',
'pmid' => 'http://www.pubmed.gov/30566872',
'doi' => '10.1016/j.celrep.2018.11.039',
'modified' => '2019-04-17 14:51:18',
'created' => '2019-04-16 12:25:30',
'ProductsPublication' => array(
[maximum depth reached]
)
),
(int) 40 => array(
'id' => '3635',
'name' => 'TIP60: an actor in acetylation of H3K4 and tumor development in breast cancer.',
'authors' => 'Judes G, Dubois L, Rifaï K, Idrissou M, Mishellany F, Pajon A, Besse S, Daures M, Degoul F, Bignon YJ, Penault-Llorca F, Bernard-Gallon D',
'description' => '<p>AIM: The acetyltransferase TIP60 is reported to be downregulated in several cancers, in particular breast cancer, but the molecular mechanisms resulting from its alteration are still unclear. MATERIALS & METHODS: In breast tumors, H3K4ac enrichment and its link with TIP60 were evaluated by chromatin immunoprecipitation-qPCR and re-chromatin immunoprecipitation techniques. To assess the biological roles of TIP60 in breast cancer, two cell lines of breast cancer, MDA-MB-231 (ER-) and MCF-7 (ER+) were transfected with shRNA specifically targeting TIP60 and injected to athymic Balb-c mice. RESULTS: We identified a potential target of TIP60, H3K4. We show that an underexpression of TIP60 could contribute to a reduction of H3K4 acetylation in breast cancer. An increase in tumor development was noted in sh-TIP60 MDA-MB-231 xenografts and a slowdown of tumor growth in sh-TIP60 MCF-7 xenografts. CONCLUSION: This is evidence that the underexpression of TIP60 observed in breast cancer can promote the tumorigenesis of ER-negative tumors.</p>',
'date' => '2018-11-01',
'pmid' => 'http://www.pubmed.gov/30324811',
'doi' => '10.2217/epi-2018-0004',
'modified' => '2019-06-07 10:29:04',
'created' => '2019-06-06 12:11:18',
'ProductsPublication' => array(
[maximum depth reached]
)
),
(int) 41 => array(
'id' => '3556',
'name' => 'PWWP2A binds distinct chromatin moieties and interacts with an MTA1-specific core NuRD complex.',
'authors' => 'Link S, Spitzer RMM, Sana M, Torrado M, Völker-Albert MC, Keilhauer EC, Burgold T, Pünzeler S, Low JKK, Lindström I, Nist A, Regnard C, Stiewe T, Hendrich B, Imhof A, Mann M, Mackay JP, Bartkuhn M, Hake SB',
'description' => '<p>Chromatin structure and function is regulated by reader proteins recognizing histone modifications and/or histone variants. We recently identified that PWWP2A tightly binds to H2A.Z-containing nucleosomes and is involved in mitotic progression and cranial-facial development. Here, using in vitro assays, we show that distinct domains of PWWP2A mediate binding to free linker DNA as well as H3K36me3 nucleosomes. In vivo, PWWP2A strongly recognizes H2A.Z-containing regulatory regions and weakly binds H3K36me3-containing gene bodies. Further, PWWP2A binds to an MTA1-specific subcomplex of the NuRD complex (M1HR), which consists solely of MTA1, HDAC1, and RBBP4/7, and excludes CHD, GATAD2 and MBD proteins. Depletion of PWWP2A leads to an increase of acetylation levels on H3K27 as well as H2A.Z, presumably by impaired chromatin recruitment of M1HR. Thus, this study identifies PWWP2A as a complex chromatin-binding protein that serves to direct the deacetylase complex M1HR to H2A.Z-containing chromatin, thereby promoting changes in histone acetylation levels.</p>',
'date' => '2018-10-16',
'pmid' => 'http://www.pubmed.gov/30327463',
'doi' => '10.1038/s41467-018-06665-5',
'modified' => '2019-07-22 09:17:39',
'created' => '2019-03-21 14:12:08',
'ProductsPublication' => array(
[maximum depth reached]
)
),
(int) 42 => array(
'id' => '3553',
'name' => 'Accurate annotation of accessible chromatin in mouse and human primordial germ cells.',
'authors' => 'Li J, Shen S, Chen J, Liu W, Li X, Zhu Q, Wang B, Chen X, Wu L, Wang M, Gu L, Wang H, Yin J, Jiang C, Gao S',
'description' => '<p>Extensive and accurate chromatin remodeling is essential during primordial germ cell (PGC) development for the perpetuation of genetic information across generations. Here, we report that distal cis-regulatory elements (CREs) marked by DNase I-hypersensitive sites (DHSs) show temporally restricted activities during mouse and human PGC development. Using DHS maps as proxy, we accurately locate the genome-wide binding sites of pluripotency transcription factors in mouse PGCs. Unexpectedly, we found that mouse female meiotic recombination hotspots can be captured by DHSs, and for the first time, we identified 12,211 recombination hotspots in mouse female PGCs. In contrast to that of meiotic female PGCs, the chromatin of mitotic-arrested male PGCs is permissive through nuclear transcription factor Y (NFY) binding in the distal regulatory regions. Furthermore, we examined the evolutionary pressure on PGC CREs, and comparative genomic analysis revealed that mouse and human PGC CREs are evolutionarily conserved and show strong conservation across the vertebrate tree outside the mammals. Therefore, our results reveal unique, temporally accessible chromatin configurations during mouse and human PGC development.</p>',
'date' => '2018-10-10',
'pmid' => 'http://www.pubmed.org/30305709',
'doi' => '10.1038/s41422-018-0096-5',
'modified' => '2019-03-25 11:04:31',
'created' => '2019-03-21 14:12:08',
'ProductsPublication' => array(
[maximum depth reached]
)
),
(int) 43 => array(
'id' => '3616',
'name' => 'Loss of H3K27me3 Imprinting in Somatic Cell Nuclear Transfer Embryos Disrupts Post-Implantation Development.',
'authors' => 'Matoba S, Wang H, Jiang L, Lu F, Iwabuchi KA, Wu X, Inoue K, Yang L, Press W, Lee JT, Ogura A, Shen L, Zhang Y',
'description' => '<p>Animal cloning can be achieved through somatic cell nuclear transfer (SCNT), although the live birth rate is relatively low. Recent studies have identified H3K9me3 in donor cells and abnormal Xist activation as epigenetic barriers that impede SCNT. Here we overcome these barriers using a combination of Xist knockout donor cells and overexpression of Kdm4 to achieve more than 20% efficiency of mouse SCNT. However, post-implantation defects and abnormal placentas were still observed, indicating that additional epigenetic barriers impede SCNT cloning. Comparative DNA methylome analysis of IVF and SCNT blastocysts identified abnormally methylated regions in SCNT embryos despite successful global reprogramming of the methylome. Strikingly, allelic transcriptomic and ChIP-seq analyses of pre-implantation SCNT embryos revealed complete loss of H3K27me3 imprinting, which may account for the postnatal developmental defects observed in SCNT embryos. Together, these results provide an efficient method for mouse cloning while paving the way for further improving SCNT efficiency.</p>',
'date' => '2018-09-06',
'pmid' => 'http://www.pubmed.gov/30033120',
'doi' => '10.1016/j.stem.2018.06.008',
'modified' => '2019-04-17 15:31:14',
'created' => '2019-04-16 13:01:51',
'ProductsPublication' => array(
[maximum depth reached]
)
),
(int) 44 => array(
'id' => '3402',
'name' => 'Polycomb repressive complex 1 shapes the nucleosome landscape but not accessibility at target genes.',
'authors' => 'King HW, Fursova NA, Blackledge NP, Klose RJ',
'description' => '<p>Polycomb group (PcG) proteins are transcriptional repressors that play important roles in regulating gene expression during animal development. In vitro experiments have shown that PcG protein complexes can compact chromatin to limit the activity of chromatin remodeling enzymes and access of the transcriptional machinery to DNA. In fitting with these ideas, gene promoters associated with PcG proteins have been reported to be less accessible than other gene promoters. However, it remains largely untested in vivo whether PcG proteins define chromatin accessibility or other chromatin features. To address this important question, we examine the chromatin accessibility and nucleosome landscape at PcG protein-bound promoters in mouse embryonic stem cells using the assay for transposase accessible chromatin (ATAC)-seq. Combined with genetic ablation strategies, we unexpectedly discover that although PcG protein-occupied gene promoters exhibit reduced accessibility, this does not rely on PcG proteins. Instead, the Polycomb repressive complex 1 (PRC1) appears to play a unique role in driving elevated nucleosome occupancy and decreased nucleosomal spacing in Polycomb chromatin domains. Our new genome-scale observations argue, in contrast to the prevailing view, that PcG proteins do not significantly affect chromatin accessibility and highlight an underappreciated complexity in the relationship between chromatin accessibility, the nucleosome landscape, and PcG-mediated transcriptional repression.</p>',
'date' => '2018-08-28',
'pmid' => 'http://www.pubmed.gov/30154222',
'doi' => '10.1101/gr.237180.118.',
'modified' => '2018-11-09 11:29:13',
'created' => '2018-11-08 12:59:45',
'ProductsPublication' => array(
[maximum depth reached]
)
),
(int) 45 => array(
'id' => '3551',
'name' => 'HIV-2/SIV viral protein X counteracts HUSH repressor complex.',
'authors' => 'Ghina Chougui, Soundasse Munir-Matloob, Roy Matkovic, Michaël M Martin, Marina Morel, Hichem Lahouassa, Marjorie Leduc, Bertha Cecilia Ramirez, Lucie Etienne and Florence Margottin-Goguet',
'description' => '<p>To evade host immune defences, human immunodeficiency viruses 1 and 2 (HIV-1 and HIV-2) have evolved auxiliary proteins that target cell restriction factors. Viral protein X (Vpx) from the HIV-2/SIVsmm lineage enhances viral infection by antagonizing SAMHD1 (refs ), but this antagonism is not sufficient to explain all Vpx phenotypes. Here, through a proteomic screen, we identified another Vpx target-HUSH (TASOR, MPP8 and periphilin)-a complex involved in position-effect variegation. HUSH downregulation by Vpx is observed in primary cells and HIV-2-infected cells. Vpx binds HUSH and induces its proteasomal degradation through the recruitment of the DCAF1 ubiquitin ligase adaptor, independently from SAMHD1 antagonism. As a consequence, Vpx is able to reactivate HIV latent proviruses, unlike Vpx mutants, which are unable to induce HUSH degradation. Although antagonism of human HUSH is not conserved among all lentiviral lineages including HIV-1, it is a feature of viral protein R (Vpr) from simian immunodeficiency viruses (SIVs) of African green monkeys and from the divergent SIV of l'Hoest's monkey, arguing in favour of an ancient lentiviral species-specific vpx/vpr gene function. Altogether, our results suggest the HUSH complex as a restriction factor, active in primary CD4 T cells and counteracted by Vpx, therefore providing a molecular link between intrinsic immunity and epigenetic control.</p>',
'date' => '2018-08-01',
'pmid' => 'http://www.pubmed.gov/29891865',
'doi' => '10.1038/s41564-018-0179-6',
'modified' => '2019-02-28 10:20:23',
'created' => '2019-02-27 12:54:44',
'ProductsPublication' => array(
[maximum depth reached]
)
),
(int) 46 => array(
'id' => '3586',
'name' => 'The transcriptional factor ZEB1 represses Syndecan 1 expression in prostate cancer.',
'authors' => 'Farfán N, Ocarez N, Castellón EA, Mejía N, de Herreros AG, Contreras HR',
'description' => '<p>Syndecan 1 (SDC-1) is a cell surface proteoglycan with a significant role in cell adhesion, maintaining epithelial integrity. SDC1 expression is inversely related to aggressiveness in prostate cancer (PCa). During epithelial to mesenchymal transition (EMT), loss of epithelial markers is mediated by transcriptional repressors such as SNAIL, SLUG, or ZEB1/2 that bind to E-box promoter sequences of specific genes. The effect of these repressors on SDC-1 expression remains unknown. Here, we demonstrated that SNAIL, SLUG and ZEB1 expressions are increased in advanced PCa, contrarily to SDC-1. SNAIL, SLUG and ZEB1 also showed an inversion to SDC-1 in prostate cell lines. ZEB1, but not SNAIL or SLUG, represses SDC-1 as demonstrated by experiments of ectopic expression in epithelial prostate cell lines. Inversely, expression of ZEB1 shRNA in PCa cell line increased SDC-1 expression. The effect of ZEB1 is transcriptional since ectopic expression of this gene represses SDC-1 promoter activity and ZEB1 binds to the SDC-1 promoter as detected by ChIP assays. An epigenetic mark associated to transcription repression H3K27me3 was bound to the same sites that ZEB1. In conclusion, this study identifies ZEB1 as a key repressor of SDC-1 during PCa progression and point to ZEB1 as a potentially diagnostic marker for PCa.</p>',
'date' => '2018-07-31',
'pmid' => 'http://www.pubmed.gov/30065348',
'doi' => '10.1038/s41598-018-29829-1',
'modified' => '2019-04-17 15:32:57',
'created' => '2019-04-16 12:25:30',
'ProductsPublication' => array(
[maximum depth reached]
)
),
(int) 47 => array(
'id' => '3381',
'name' => 'TSPYL2 Regulates the Expression of EZH2 Target Genes in Neurons',
'authors' => 'Hang Liu et al.',
'description' => '<p><em class="EmphasisTypeItalic ">Testis-specific protein</em>, <em class="EmphasisTypeItalic ">Y-encoded-like 2</em> (TSPYL2) is an X-linked gene in the locus for several neurodevelopmental disorders. We have previously shown that <em class="EmphasisTypeItalic ">Tspyl2</em> knockout mice had impaired learning and sensorimotor gating, and TSPYL2 facilitates the expression of <em class="EmphasisTypeItalic ">Grin2a</em> and <em class="EmphasisTypeItalic ">Grin2b</em> through interaction with CREB-binding protein. To identify other genes regulated by TSPYL2, here, we showed that <em class="EmphasisTypeItalic ">Tspyl2</em> knockout mice had an increased level of H3K27 trimethylation (H3K27me3) in the hippocampus, and TSPYL2 interacted with the H3K27 methyltransferase enhancer of zeste 2 (EZH2). We performed chromatin immunoprecipitation (ChIP)-sequencing in primary hippocampal neurons and divided all Refseq genes by k-mean clustering into four clusters from highest level of H3K27me3 to unmarked. We confirmed that mutant neurons had an increased level of H3K27me3 in cluster 1 genes, which consist of known EZH2 target genes important in development. We detected significantly reduced expression of genes including <em class="EmphasisTypeItalic ">Gbx2</em> and <em class="EmphasisTypeItalic ">Prss16</em> from cluster 1 and <em class="EmphasisTypeItalic ">Acvrl1</em>, <em class="EmphasisTypeItalic ">Bdnf</em>, <em class="EmphasisTypeItalic ">Egr3</em>, <em class="EmphasisTypeItalic ">Grin2c</em>, and <em class="EmphasisTypeItalic ">Igf1</em> from cluster 2 in the mutant. In support of a dynamic role of EZH2 in repressing marked synaptic genes, the specific EZH2 inhibitor GSK126 significantly upregulated, while the demethylase inhibitor GSKJ4 downregulated the expression of <em class="EmphasisTypeItalic ">Egr3</em> and <em class="EmphasisTypeItalic ">Grin2c</em>. GSK126 also upregulated the expression of <em class="EmphasisTypeItalic ">Bdnf</em> in mutant primary neurons. Finally, ChIP showed that hemagglutinin-tagged TSPYL2 co-existed with EZH2 in target promoters in neuroblastoma cells. Taken together, our data suggest that TSPYL2 is recruited to promoters of specific EZH2 target genes in neurons, and enhances their expression for proper neuronal maturation and function.</p>',
'date' => '2018-07-26',
'pmid' => 'https://link.springer.com/article/10.1007/s12035-018-1238-y',
'doi' => '',
'modified' => '2018-07-31 10:01:24',
'created' => '2018-07-31 10:01:24',
'ProductsPublication' => array(
[maximum depth reached]
)
),
(int) 48 => array(
'id' => '3519',
'name' => 'Forskolin Sensitizes Human Acute Myeloid Leukemia Cells to H3K27me2/3 Demethylases GSKJ4 Inhibitor via Protein Kinase A.',
'authors' => 'Illiano M, Conte M, Sapio L, Nebbioso A, Spina A, Altucci L, Naviglio S',
'description' => '<p>Acute myeloid leukemia (AML) is an aggressive hematological malignancy occurring very often in older adults, with poor prognosis depending on both rapid disease progression and drug resistance occurrence. Therefore, new therapeutic approaches are demanded. Epigenetic marks play a relevant role in AML. GSKJ4 is a novel inhibitor of the histone demethylases JMJD3 and UTX. To note GSKJ4 has been recently shown to act as a potent small molecule inhibitor of the proliferation in many cancer cell types. On the other hand, forskolin, a natural cAMP raising compound, used for a long time in traditional medicine and considered safe also in recent studies, is emerging as a very interesting molecule for possible use in cancer therapy. Here, we investigate the effects of forskolin on the sensitivity of human leukemia U937 cells to GSKJ4 through flow cytometry-based assays (cell-cycle progression and cell death), cell number counting, and immunoblotting experiments. We provide evidence that forskolin markedly potentiates GSKJ4-induced antiproliferative effects by apoptotic cell death induction, accompanied by a dramatic BCL2 protein down-regulation as well as caspase 3 activation and PARP protein cleavage. Comparable effects are observed with the phosphodiesterase inhibitor IBMX and 8-Br-cAMP analogous, but not by using 8-pCPT-2'-O-Me-cAMP Epac activator. Moreover, the forskolin-induced enhancement of sensitivity to GSKJ4 is counteracted by pre-treatment with Protein Kinase A (PKA) inhibitors. Altogether, our data strongly suggest that forskolin sensitizes U937 cells to GSKJ4 inhibitor via a cAMP/PKA-mediated mechanism. Our findings provide initial evidence of anticancer activity induced by forskolin/GSKJ4 combination in leukemia cells and underline the potential for use of forskolin and GSKJ4 in the development of innovative and effective therapeutic approaches for AML treatment.</p>',
'date' => '2018-07-20',
'pmid' => 'http://www.pubmed.gov/30079022',
'doi' => '10.3389/fphar.2018.00792',
'modified' => '2019-02-28 10:23:58',
'created' => '2019-02-27 12:54:44',
'ProductsPublication' => array(
[maximum depth reached]
)
),
(int) 49 => array(
'id' => '3425',
'name' => 'HMGB2 Loss upon Senescence Entry Disrupts Genomic Organization and Induces CTCF Clustering across Cell Types.',
'authors' => 'Zirkel A, Nikolic M, Sofiadis K, Mallm JP, Brackley CA, Gothe H, Drechsel O, Becker C, Altmüller J, Josipovic N, Georgomanolis T, Brant L, Franzen J, Koker M, Gusmao EG, Costa IG, Ullrich RT, Wagner W, Roukos V, Nürnberg P, Marenduzzo D, Rippe K, Papanton',
'description' => '<p>Processes like cellular senescence are characterized by complex events giving rise to heterogeneous cell populations. However, the early molecular events driving this cascade remain elusive. We hypothesized that senescence entry is tri
