Diagenode

IP-Star Compact

101 publications found.

Epigenetic dosage identifies two major and functionally distinct beta cells ubtypes.
Published: March, 2023

Abstract: The mechanisms that specify and stabilize cell subtypes remain poorly understood. Here, we identify two major subtypes of pancreatic β cells based on histone mark heterogeneity (beta HI and beta LO). Beta HI cells exhibit 4-fold higher...
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K27M in canonical and noncanonical H3 variants occurs in distinctoligodendroglial cell lineages in brain midline gliomas.
Published: December, 2022

Abstract: Canonical (H3.1/H3.2) and noncanonical (H3.3) histone 3 K27M-mutant gliomas have unique spatiotemporal distributions, partner alterations and molecular profiles. The contribution of the cell of origin to these differences has been challenging to u...
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Vitamin D receptor and STAT6 interactome governs oesophagealepithelial barrier responses to IL-13 signalling.
Published: August, 2022

Abstract: OBJECTIVE: The contribution of vitamin D (VD) deficiency to the pathogenesis of allergic diseases remains elusive. We aimed to define the impact of VD on oesophageal allergic inflammation. DESIGN: We assessed the genomic distribution and function ...
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A genome-wide screen reveals new regulators of the 2-cell-like cell state
Published: June, 2022

Abstract: In mammals, only the zygote and blastomeres of the early embryo are fully totipotent. This totipotency is mirrored in vitro by mouse "2-cell-like cells" (2CLCs), which appear at low frequency in cultures of Embryonic Stem cells (ESCs). Because tot...
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GATA6 is predicted to regulate DNA methylation in an in vitro model ofhuman hepatocyte differentiation.
Published: May, 2022

Abstract: Hepatocytes are the dominant cell type in the human liver, with functions in metabolism, detoxification, and producing secreted proteins. Although gene regulation and master transcription factors involved in the hepatocyte differentiation have bee...
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Effects of GSK-J4 on JMJD3 Histone Demethylase in Mouse Prostate Cancer Xenografts
Published: May, 2022

Abstract: 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 ...
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Comprehensive characterization of the epigenetic landscape in Multiple Myeloma
Published: January, 2022

Abstract: Background: Human multiple myeloma (MM) cell lines (HMCLs) have been widely used to understand themolecular processes that drive MM biology. Epigenetic modifications are involved in MM development,progression, and drug resistance. A comprehensive ...
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Comprehensive characterization of the epigenetic landscape in Multiple Myeloma
Published: January, 2022

Abstract: Background: Human multiple myeloma (MM) cell lines (HMCLs) have been widely used to understand the molecular processes that drive MM biology. Epigenetic modifications are involved in MM development, progression, and drug resistance. A comprehensiv...
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Sp1-Induced SETDB1 Overexpression Transcriptionally InhibitsHPGD in a β-Catenin-Dependent Manner and Promotes theProliferation and Metastasis of Gastric Cancer
Published: January, 2022

Abstract: Gastric cancer (GC) has high morbidity and mortality, the cure rate of surgical treatment and drug chemotherapy is not ideal. Therefore, development of new treatment strategies is necessary. We aimed to identify the mechanism underlying Sp1 regula...
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Chemokine switch regulated by TGF-β1 in cancer-associated fibroblastsubsets determines the efficacy of chemo-immunotherapy.
Published: January, 2022

Abstract: 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-re...
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Rhesus macaques self-curing from a schistosome infection can displaycomplete immunity to challenge
Published: October, 2021

Abstract: The rhesus macaque provides a unique model of acquired immunity against schistosomes, which afflict \>200 million people worldwide. By monitoring bloodstream levels of parasite-gut-derived antigen, we show that from week 10 onwards an establish...
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Lasp1 regulates adherens junction dynamics and fibroblast transformationin destructive arthritis
Published: June, 2021

Abstract: The LIM and SH3 domain protein 1 (Lasp1) was originally cloned from metastatic breast cancer and characterised as an adaptor molecule associated with tumourigenesis and cancer cell invasion. However, the regulation of Lasp1 and its function in the...
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The insecticide permethrin induces transgenerational behavioral changeslinked to transcriptomic and epigenetic alterations in zebrafish (Daniorerio).
Published: March, 2021

Abstract: The pyrethroid insecticide permethrin is widely used for agricultural and domestic purposes. Previous data indicated that it acts as a developmental neurotoxicant and can induce transgenerational effects in non-target organisms. However, associate...
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Chromatin dysregulation associated with NSD1 mutation in head and necksquamous cell carcinoma.
Published: February, 2021

Abstract: Chromatin dysregulation has emerged as an important mechanism of oncogenesis. To develop targeted treatments, it is important to understand the transcriptomic consequences of mutations in chromatin modifier genes. Recently, mutations in the histon...
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A Tumor Suppressor Enhancer of PTEN in T-cell development and leukemia
Published: January, 2021

Abstract: Long-range oncogenic enhancers play an important role in cancer. Yet, whether similar regulation of tumor suppressor genes is relevant remains unclear. Loss of expression of PTEN is associated with the pathogenesis of various cancers, including T-...
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Postoperative abdominal sepsis induces selective and persistent changes inCTCF binding within the MHC-II region of human monocytes.
Published: January, 2021

Abstract: BACKGROUND: Postoperative abdominal infections belong to the most common triggers of sepsis and septic shock in intensive care units worldwide. While monocytes play a central role in mediating the initial host response to infections, sepsis-induce...
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Histone H3.3G34-Mutant Interneuron Progenitors Co-opt PDGFRA for Gliomagenesis.
Published: December, 2020

Abstract: Histone H3.3 glycine 34 to arginine/valine (G34R/V) mutations drive deadly gliomas and show exquisite regional and temporal specificity, suggesting a developmental context permissive to their effects. Here we show that 50\% of G34R/V tumors (n&nbs...
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H3K27M in Gliomas Causes a One-Step Decrease in H3K27 Methylation andReduced Spreading within the Constraints of H3K36 Methylation.
Published: November, 2020

Abstract: The discovery of H3K27M mutations in pediatric gliomas marked a new chapter in cancer epigenomics. Numerous studies have investigated the effect of this mutation on H3K27 trimethylation, but only recently have we started to realize its additional ...
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Digging Deeper into Breast Cancer Epigenetics: Insights from ChemicalInhibition of Histone Acetyltransferase TIP60 .
Published: October, 2020

Abstract: Breast cancer is often sporadic due to several factors. Among them, the deregulation of epigenetic proteins may be involved. TIP60 or KAT5 is an acetyltransferase that regulates gene transcription through the chromatin structure. This pleiotropic ...
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Super-enhancer switching drives a burst in gene expression at themitosis-to-meiosis transition.
Published: October, 2020

Abstract: Owing to bursts in the expression of thousands of germline-specific genes, the testis has the most diverse and complex transcriptome of all organs. By analyzing the male germline of mice, we demonstrate that the genome-wide reorganization of super...
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Epigenetic regulation of the lineage specificity of primary human dermallymphatic and blood vascular endothelial cells.
Published: September, 2020

Abstract: Lymphatic and blood vascular endothelial cells (ECs) share several molecular and developmental features. However, these two cell types possess distinct phenotypic signatures, reflecting their different biological functions. Despite significant adv...
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Human papillomavirus type 38 alters wild-type p53 activity to promote cellproliferation via the downregulation of integrin alpha 1 expression.
Published: August, 2020

Abstract: Tumor suppressors can exert pro-proliferation functions in specific contexts. In the beta human papillomavirus type 38 (HPV38) experimental model, the viral proteins E6 and E7 promote accumulation of a wild-type (WT) p53 form in human keratinocyte...
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2,4-dienoyl-CoA reductase regulates lipid homeostasis in treatment-resistant prostate cancer.
Published: May, 2020

Abstract: Despite the clinical success of Androgen Receptor (AR)-targeted therapies, reactivation of AR signalling remains the main driver of castration-resistant prostate cancer (CRPC) progression. In this study, we perform a comprehensive unbiased charact...
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Genome-Wide DNA Methylation Profiling in Early Stage I Lung Adenocarcinoma Reveals Predictive Aberrant Methylation in the Promoter Region of the Long Noncoding RNA PLUT: An Exploratory Study.
Published: April, 2020

Abstract: INTRODUCTION: Surgical procedure is the treatment of choice in early stage I lung adenocarcinoma. However, a considerable number of patients experience recurrence within the first 2 years after complete resection. Suitable prognostic biomarkers th...
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Multi-omic analysis of gametogenesis reveals a novel signature at the promoters and distal enhancers of active genes.
Published: March, 2020

Abstract: Epigenetic regulation of gene expression is tightly controlled by the dynamic modification of histones by chemical groups, the diversity of which has largely expanded over the past decade with the discovery of lysine acylations, catalyzed from acy...
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SMaSH: Sample matching using SNPs in humans.
Published: December, 2019

Abstract: BACKGROUND: Inadvertent sample swaps are a real threat to data quality in any medium to large scale omics studies. While matches between samples from the same individual can in principle be identified from a few well characterized single nucleotid...
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Functionally Annotating Regulatory Elements in the Equine Genome Using Histone Mark ChIP-Seq.
Published: December, 2019

Abstract: One of the primary aims of the Functional Annotation of ANimal Genomes (FAANG) initiative is to characterize tissue-specific regulation within animal genomes. To this end, we used chromatin immunoprecipitation followed by sequencing (ChIP-Seq) to ...
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Methionine metabolism in health and cancer: a nexus of diet and precisionmedicine.
Published: November, 2019

Abstract: Methionine uptake and metabolism is involved in a host of cellular functions including methylation reactions, redox maintenance, polyamine synthesis and coupling to folate metabolism, thus coordinating nucleotide and redox status. Each of these fu...
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Reactivation of super-enhancers by KLF4 in human Head and Neck Squamous Cell Carcinoma.
Published: September, 2019

Abstract: Head and neck squamous cell carcinoma (HNSCC) is a disease of significant morbidity and mortality and rarely diagnosed in early stages. Despite extensive genetic and genomic characterization, targeted therapeutics and diagnostic markers of HNSCC a...
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The histone mark H3K36me2 recruits DNMT3A and shapes the intergenic DNA methylation landscape.
Published: September, 2019

Abstract: Enzymes that catalyse CpG methylation in DNA, including the DNA methyltransferases 1 (DNMT1), 3A (DNMT3A) and 3B (DNMT3B), are indispensable for mammalian tissue development and homeostasis. They are also implicated in human developmental disorder...
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Human mitochondrial DNA is extensively methylated in a non-CpG context
Published: August, 2019

Abstract: Mitochondrial dysfunction plays critical roles in cancer development and related therapeutic response; however, exact molecular mechanisms remain unclear. Recently, alongside the discovery of mitochondrial-specific DNA methyltransferases, global a...
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Development and epigenetic plasticity of murine Müller glia.
Published: July, 2019

Abstract: The ability to regenerate the entire retina and restore lost sight after injury is found in some species and relies mostly on the epigenetic plasticity of Müller glia. To understand the role of mammalian Müller glia as a source of progen...
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Pervasive H3K27 Acetylation Leads to ERV Expression and a Therapeutic Vulnerability in H3K27M Gliomas.
Published: May, 2019

Abstract: High-grade gliomas defined by histone 3 K27M driver mutations exhibit global loss of H3K27 trimethylation and reciprocal gain of H3K27 acetylation, respectively shaping repressive and active chromatin landscapes. We generated tumor-derived isogeni...
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Guidelines for optimized gene knockout using CRISPR/Cas9
Published: May, 2019

Abstract: CRISPR/Cas9 technology has evolved as the most powerful approach to generate genetic models both for fundamental and preclinical research. Despite its apparent simplicity, the outcome of a genome-editing experiment can be substantially impacted by...
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Interferon signature in patients with STAT1 gain-of-function mutation is epigenetically determined.
Published: May, 2019

Abstract: STAT1 gain-of-function (GOF) variants lead to defective Th17 cell development and chronic mucocutaneous candidiasis (CMC), but frequently also to autoimmunity. Stimulation of cells with STAT1 inducing cytokines like interferons (IFN) result i...
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Repression of Germline Genes in Somatic Tissues by H3K9 Dimethylation of Their Promoters.
Published: May, 2019

Abstract: Repression of germline-promoting genes in somatic cells is critical for somatic development and function. To study how germline genes are repressed in somatic tissues, we analyzed key histone modifications in three synMuv B mutants, , , and -all o...
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H3K27M induces defective chromatin spread of PRC2-mediated repressive H3K27me2/me3 and is essential for glioma tumorigenesis.
Published: March, 2019

Abstract: Lys-27-Met mutations in histone 3 genes (H3K27M) characterize a subgroup of deadly gliomas and decrease genome-wide H3K27 trimethylation. Here we use primary H3K27M tumor lines and isogenic CRISPR-edited controls to assess H3K27M effects in vitro ...
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Genetic, Inflammatory, and Epithelial Cell Differentiation Factors Control Expression of Human Calpain-14.
Published: March, 2019

Abstract: Eosinophilic esophagitis (EoE) is a chronic, food-driven allergic disease resulting in eosinophilic esophageal inflammation. We recently found that EoE susceptibility is associated with genetic variants in the promoter of , a gene with reported es...
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The epigenetic basis for the impaired ability of adult murine retinal pigment epithelium cells to regenerate retinal tissue.
Published: March, 2019

Abstract: The epigenetic plasticity of amphibian retinal pigment epithelium (RPE) allows them to regenerate the entire retina, a trait known to be absent in mammals. In this study, we investigated the epigenetic plasticity of adult murine RPE to identify po...
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EZH2 is overexpressed in transitional preplasmablasts and is involved in human plasma cell differentiation.
Published: February, 2019

Abstract: Plasma cells (PCs) play a major role in the defense of the host organism against pathogens. We have shown that PC generation can be modeled using multi-step culture systems that reproduce the sequential cell differentiation occurring in vivo. Usin...
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Protocols for Genetic and Epigenetic Studies of Rare Diseases Affecting Dental Tissues.
Published: January, 2019

Abstract: This chapter describes methods related to the diagnosis of genetic dental diseases. Based on the present knowledge, clinical phenotyping and next-generation sequencing techniques are discussed. Methods necessary for Sanger sequencing, multiplex li...
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TIP60: an actor in acetylation of H3K4 and tumor development in breast cancer.
Published: November, 2018

Abstract: 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 enric...
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Caenorhabditis elegans sperm carry a histone-based epigenetic memory of both spermatogenesis and oogenesis.
Published: October, 2018

Abstract: Paternal contributions to epigenetic inheritance are not well understood. Paternal contributions via marked nucleosomes are particularly understudied, in part because sperm in some organisms replace the majority of nucleosome packaging with protam...
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PRC2 targeting is a therapeutic strategy for EZ score defined high-risk multiple myeloma patients and overcome resistance to IMiDs.
Published: October, 2018

Abstract: BACKGROUND: Multiple myeloma (MM) is a malignant plasma cell disease with a poor survival, characterized by the accumulation of myeloma cells (MMCs) within the bone marrow. Epigenetic modifications in MM are associated not only with cancer develop...
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Atopic asthma after rhinovirus-induced wheezing is associated with DNA methylation change in the SMAD3 gene promoter.
Published: August, 2018

Abstract: Children with rhinovirus-induced severe early wheezing have an increased risk of developing asthma later in life. The exact molecular mechanisms for this association are still mostly unknown. To identify potential changes in the transcriptional an...
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An Integrated and Semiautomated Microscaled Approach to Profile Cis-Regulatory Elements by Histone Modification ChIP-Seq for Large-Scale Epigenetic Studies.
Published: June, 2018

Abstract: Chromatin immunoprecipitation followed by sequencing (ChIP-Seq) is the preferred approach to map histone modifications and identify cis-regulatory DNA elements throughout the genome. Multiple methods have been described to increase the efficiency ...
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An improved assembly and annotation of the melon (Cucumis melo L.) reference genome.
Published: May, 2018

Abstract: We report an improved assembly (v3.6.1) of the melon (Cucumis melo L.) genome and a new genome annotation (v4.0). The optical mapping approach allowed correcting the order and the orientation of 21 previous scaffolds and permitted to correctly def...
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Insulin promoter in human pancreatic β cells contacts diabetes susceptibility loci and regulates genes affecting insulin metabolism.
Published: May, 2018

Abstract: Both type 1 and type 2 diabetes involve a complex interplay between genetic, epigenetic, and environmental factors. Our laboratory has been interested in the physical interactions, in nuclei of human pancreatic β cells, between the insulin ( ...
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A new metabolic gene signature in prostate cancer regulated by JMJD3 and EZH2.
Published: May, 2018

Abstract: Histone methylation is essential for gene expression control. Trimethylated lysine 27 of histone 3 (H3K27me3) is controlled by the balance between the activities of JMJD3 demethylase and EZH2 methyltransferase. This epigenetic mark has been shown ...
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Molecular Signatures of Regression of the Canine Transmissible Venereal Tumor.
Published: April, 2018

Abstract: The canine transmissible venereal tumor (CTVT) is a clonally transmissible cancer that regresses spontaneously or after treatment with vincristine, but we know little about the regression mechanisms. We performed global transcriptional, methylatio...
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Effects of developmental lead exposure on the hippocampal methylome: Influences of sex and timing and level of exposure
Published: March, 2018

Abstract: Developmental lead (Pb) exposure results in persistent cognitive/behavioral impairments as well as an elevated risk for developing a variety of diseases in later life. Environmental exposures during development can result in a variety of epigeneti...
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The histone code reader Spin1 controls skeletal muscle development
Published: November, 2017

Abstract: While several studies correlated increased expression of the histone code reader Spin1 with tumor formation or growth, little is known about physiological functions of the protein. We generated Spin1M5 mice with ablation of Spin1 in myoblast precu...
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Saliva as a Blood Alternative for Genome-Wide DNA Methylation Profiling by Methylated DNA Immunoprecipitation (MeDIP) Sequencing
Published: October, 2017

Abstract: Background: Interrogation of DNA methylation profiles hold promise for improved diagnostics, as well as the delineation of the aetiology for common human diseases. However, as the primary tissue of the disease is often inaccessible without complic...
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Discovery of a selective catalytic p300/CBP inhibitor that targets lineage-specific tumours.
Published: October, 2017

Abstract: The dynamic and reversible acetylation of proteins, catalysed by histone acetyltransferases (HATs) and histone deacetylases (HDACs), is a major epigenetic regulatory mechanism of gene transcription and is associated with multiple diseases. Histone...
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BET-bromodomain inhibitors modulate epigenetic patterns at the diacylglycerol kinase alpha enhancer associated with radiation-induced fibrosis.
Published: October, 2017

Abstract: BACKGROUND AND PURPOSE: Fibrosis is a frequent adverse effect of radiotherapy and no effective treatments are currently available to prevent or reverse fibrotic disease. We have previously identified altered epigenetic patterns at a gene enhancer...
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FOXF1 transcription factor promotes lung regeneration after partial pneumonectomy
Published: September, 2017

Abstract: FOXF1, a member of the forkhead box family of transcription factors, has been previously shown to be critical for lung development, homeostasis, and injury responses. However, the role of FOXF1 in lung regeneration is unknown. Herein, we performed...
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Genome-wide screen for differentially methylated long noncoding RNAs identifies Esrp2 and lncRNA Esrp2-as regulated by enhancer DNA methylation with prognostic relevance for human breast cancer
Published: July, 2017

Abstract: The majority of long noncoding RNAs (lncRNAs) is still poorly characterized with respect to function, interactions with protein-coding genes, and mechanisms that regulate their expression. As for protein-coding RNAs, epigenetic deregulation of lnc...
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TET-Catalyzed 5-Hydroxymethylation Precedes HNF4A Promoter Choice during Differentiation of Bipotent Liver Progenitors
Published: July, 2017

Abstract: Understanding the processes that govern liver progenitor cell differentiation has important implications for the design of strategies targeting chronic liver diseases, whereby regeneration of liver tissue is critical. Although DNA methylation (5mC...
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Natural and induced loss of function mutations in SlMBP21 MADS-box gene led to jointless-2 phenotype in tomato
Published: June, 2017

Abstract: Abscission is the mechanism by which plants disconnect unfertilized flowers, ripe fruits, senescent or diseased organs from the plant. In tomato, pedicel abscission is an important agronomic factor that controls yield and post-harvest fruit qualit...
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Performance of four modern whole genome amplification methods for copy number variant detection in single cells
Published: June, 2017

Abstract: Whole genome amplification (WGA) has become an invaluable tool to perform copy number variation (CNV) detection in single, or a limited number of cells. Unfortunately, current WGA methods introduce representation bias that limits the detection of ...
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DNMT and HDAC inhibitors induce cryptic transcription start sites encoded in long terminal repeats
Published: June, 2017

Abstract: Several mechanisms of action have been proposed for DNA methyltransferase and histone deacetylase inhibitors (DNMTi and HDACi), primarily based on candidate-gene approaches. However, less is known about their genome-wide transcriptional and epigen...
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Histone deacetylase inhibitors potentiate photodynamic therapy in colon cancer cells marked by chromatin-mediated epigenetic regulation of CDKN1A
Published: June, 2017

Abstract: Background Hypericin-mediated photodynamic therapy (HY-PDT) has recently captured increased attention as an alternative minimally invasive anticancer treatment, although cancer cells may acquire resistance. Therefore, combination treatments m...
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ASXL2 is essential for haematopoiesis and acts as a haploinsufficient tumour suppressor in leukemia
Published: May, 2017

Abstract: Additional sex combs-like (ASXL) proteins are mammalian homologues of additional sex combs (Asx), a regulator of trithorax and polycomb function in Drosophila. While there has been great interest in ASXL1 due to its frequent mutation in leukemia, ...
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Evolutionary re-wiring of p63 and the epigenomic regulatory landscape in keratinocytes and its potential implications on species-specific gene expression and phenotypes
Published: May, 2017

Abstract: Although epidermal keratinocyte development and differentiation proceeds in similar fashion between humans and mice, evolutionary pressures have also wrought significant species-specific physiological differences. These differences between species...
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DNA breaks and chromatin structural changes enhance the transcription of Autoimmune Regulator target genes
Published: April, 2017

Abstract: The autoimmune regulator (AIRE) protein is the key factor in thymic negative selection of autoreactive T cells by promoting the ectopic expression of tissue-specific genes in the thymic medullary epithelium. Mutations in AIRE cause a monogenic aut...
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Global analysis of H3K27me3 as an epigenetic marker in prostate cancer progression
Published: April, 2017

Abstract: BACKGROUND: H3K27me3 histone marks shape the inhibition of gene transcription. In prostate cancer, the deregulation of H3K27me3 marks might play a role in prostate tumor progression. METHODS: We investigated genome-wide H3K27me3 histone methy...
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Functional variation in allelic methylomes underscores a strong genetic contribution and reveals novel epigenetic alterations in the human epigenome.
Published: March, 2017

Abstract: BACKGROUND: The functional impact of genetic variation has been extensively surveyed, revealing that genetic changes correlated to phenotypes lie mostly in non-coding genomic regions. Studies have linked allele-specific genetic changes to gene ...
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Crebbp loss cooperates with Bcl2 over-expression to promote lymphoma in mice
Published: March, 2017

Abstract: CREBBP is targeted by inactivating mutations in follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL). Here, we provide evidence from transgenic mouse models that Crebbp deletion results in deficits in B-cell development and can coope...
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Inactivation of Lsd1 triggers senescence in trophoblast stem cells by induction of Sirt4
Published: February, 2017

Abstract: Coordination of energy metabolism is essential for homeostasis of stem cells, whereas an imbalance in energy homeostasis causes disease and accelerated aging. Here we show that deletion or enzymatic inactivation of lysine-specific demethylase 1 (L...
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Rapid Recall Ability of Memory T cells is Encoded in their Epigenome
Published: January, 2017

Abstract: Even though T-cell receptor (TCR) stimulation together with co-stimulation is sufficient for the activation of both naïve and memory T cells, the memory cells are capable of producing lineage specific cytokines much more rapidly than the na&i...
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Evaluating the Feasibility of DNA Methylation Analyses Using Long-Term Archived Brain Formalin-Fixed Paraffin-Embedded Samples
Published: December, 2016

Abstract: We here characterize the usability of archival formalin-fixed paraffin-embedded (FFPE) brain tissue as a resource for genetic and DNA methylation analyses with potential relevance for brain-manifested diseases. We analyzed FFPE samples from The Br...
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Distinct and Shared Determinants of Cardiomyocyte Contractility in Multi-Lineage Competent Ethnically Diverse Human iPSCs
Published: December, 2016

Abstract: The realization of personalized medicine through human induced pluripotent stem cell (iPSC) technology can be advanced by transcriptomics, epigenomics, and bioinformatics that inform on genetic pathways directing tissue development and function. W...
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Genome-wide epigenomic profiling for biomarker discovery
Published: November, 2016

Abstract: A myriad of diseases is caused or characterized by alteration of epigenetic patterns, including changes in DNA methylation, post-translational histone modifications, or chromatin structure. These changes of the epigenome represent a highly interes...
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Genetic Drivers of Epigenetic and Transcriptional Variation in Human Immune Cells
Published: November, 2016

Abstract: Characterizing the multifaceted contribution of genetic and epigenetic factors to disease phenotypes is a major challenge in human genetics and medicine. We carried out high-resolution genetic, epigenetic, and transcriptomic profiling in thr...
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RNA polymerase II promoter-proximal pausing in mammalian long non-coding genes
Published: August, 2016

Abstract: Mammalian genomes encode a large number of non-coding RNAs (ncRNAs) that greatly exceed mRNA genes. While the physiological and pathological roles of ncRNAs have been increasingly understood, the mechanisms of regulation of ncRNA expression are le...
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Epigenetic dynamics of monocyte-to-macrophage differentiation
Published: July, 2016

Abstract: BACKGROUND: Monocyte-to-macrophage differentiation involves major biochemical and structural changes. In order to elucidate the role of gene regulatory changes during this process, we used high-throughput sequencing to analyze the complete tran...
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H3K4 acetylation, H3K9 acetylation and H3K27 methylation in breast tumor molecular subtypes
Published: July, 2016

Abstract: AIM: Here, we investigated how the St Gallen breast molecular subtypes displayed distinct histone H3 profiles. PATIENTS & METHODS: 192 breast tumors divided into five St Gallen molecular subtypes (luminal A, luminal B HER2-, luminal B HER...
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Characterization of the replication timing program of 6 human model cell lines
Published: July, 2016

Abstract: During the S-phase, the DNA replication process is finely orchestrated and regulated by two programs: the spatial program that determines where replication will start in the genome (Cadoret et al. (2008 Oct 14), Cayrou et al. (2011 Sep), Picard et...
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H4K5 histone acetylation of BRG1 is associated with heroin administration rather than addiction
Published: July, 2016

Abstract: Diacetylmorphine hydrochloride (heroin) addiction is a chronic relapsing brain disorder that is a heavy public health burden worldwide. Brm/SWI2-related gene-1 (BRG1) is a tumor suppressor gene that can influence embryogenesis and the development ...
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Aberrant DNA methylation of WNT pathway genes in the development and progression of CIMP-negative colorectal cancer.
Published: May, 2016

Abstract: The WNT signaling pathway has an essential role in colorectal carcinogenesis and progression, which involves a cascade of genetic and epigenetic changes. We aimed to analyze DNA methylation affecting the WNT pathway genes in colorectal carcinogene...
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Genome-wide non-CpG methylation of the host genome during M. tuberculosis infection
Published: April, 2016

Abstract: A mammalian cell utilizes DNA methylation to modulate gene expression in response to environmental changes during development and differentiation. Aberrant DNA methylation changes as a correlate to diseased states like cancer, neurodegenerative co...
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The Nuclear Ribonucleoprotein SmD1 Interplays with Splicing, RNA Quality Control, and Posttranscriptional Gene Silencing in Arabidopsis
Published: February, 2016

Abstract: RNA quality control (RQC) eliminates aberrant RNAs based on their atypical structure, whereas posttranscriptional gene silencing (PTGS) eliminates both aberrant and functional RNAs through the sequence-specific action of short interfering RNAs (si...
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The chloroplastic DEVH-box RNA helicase INCREASED SIZE EXCLUSION LIMIT 2 involved in plasmodesmata regulation is required for group II intron splicing
Published: January, 2016

Abstract: INCREASED SIZE EXCLUSION LIMIT 2 (ISE2) encodes a putative DEVH-box RNA helicase originally identified through a genetic screening for Arabidopsis mutants altered in plasmodesmata (PD) aperture. Depletion of ISE2 also affects chloroplasts activity...
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Standardizing chromatin research: a simple and universal method for ChIP-seq
Published: December, 2015

Abstract: Here we demonstrate that harmonization of ChIP-seq workflows across cell types and conditions is possible when obtaining chromatin from properly isolated nuclei. We established an ultrasound-based nuclei extraction method (Nuclei Extraction b...
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A highly conserved NF-κB-responsive enhancer is critical for thymic expression of Aire in mice
Published: December, 2015

Abstract: Autoimmune regulator (Aire) has a unique expression pattern in thymic medullary epithelial cells (mTECs), in which it plays a critical role in the activation of tissue-specific antigens. The expression of Aire in mTECs is activated by receptor act...
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Progressive Chromatin Condensation and H3K9 Methylation Regulate the Differentiation of Embryonic and Hematopoietic Stem Cells
Published: November, 2015

Abstract: Epigenetic regulation serves as the basis for stem cell differentiation into distinct cell types, but it is unclear how global epigenetic changes are regulated during this process. Here, we tested the hypothesis that global chromatin organization ...
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Loss of BAP1 function leads to EZH2-dependent transformation
Published: October, 2015

Abstract: The tumor suppressors BAP1 and ASXL1 interact to form a polycomb deubiquitinase complex that removes monoubiquitin from histone H2A lysine 119 (H2AK119Ub). However, BAP1 and ASXL1 are mutated in distinct cancer types, consistent with independent r...
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Comparative analysis of anti-viral transcriptomics reveals novel effects of influenza immune antagonism
Published: August, 2015

Abstract: BACKGROUND: Comparative analysis of genome-wide expression profiles are increasingly being used to study virus-specific host interactions. In order to gain mechanistic insights, gene expression profiles can be combined with information on DNA-b...
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The interaction of mycobacterial protein Rv2966c with host chromatin is mediated through non-CpG methylation and histone H3/H4 binding.
Published: April, 2015

Abstract: To effectively modulate the gene expression within an infected mammalian cell, the pathogen Mycobacterium tuberculosis would need to bring about epigenetic modifications at appropriate genomic loci. Working on this hypothesis, we show in this stud...
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An automated method for efficient, accurate and reproducible construction of RNA-seq libraries.
Published: April, 2015

Abstract: BACKGROUND: Integration of RNA-seq expression data with knowledge on chromatin accessibility, histone modifications, DNA methylation, and transcription factor binding has been instrumental for the unveiling of cell-specific local and long-range re...
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Bacterial Infection Remodels the DNA Methylation Landscape of Human Dendritic Cells
Published: March, 2015

Abstract: DNA methylation is thought to be robust to environmental perturbations on a short time scale. Here, we challenge that view by demonstrating that the infection of human dendritic cells (DCs) with a pathogenic bacteria is associated with rapid chang...
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The histone demethylase enzyme KDM3A is a key estrogen receptor regulator in breast cancer.
Published: January, 2015

Abstract: Endocrine therapy has successfully been used to treat estrogen receptor (ER)-positive breast cancer, but this invariably fails with cancers becoming refractory to treatment. Emerging evidence has suggested that fluctuations in ER co-regulatory pro...
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A Novel Role for Kruppel-like Factor 14 (KLF14) in T-Regulatory Cell Differentiation
Published: December, 2014

Abstract: Background & Aims Kruppel-like Factor 14 (KLF14) proteins function as epigenetic reprogramming factors during cell differentiation in many cell populations and in engineered induced pluripotent stem cells. In this study, we determined the func...
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Long noncoding RNA modulates alternative splicing regulators in Arabidopsis.
Published: July, 2014

Abstract: Alternative splicing (AS) of pre-mRNA represents a major mechanism underlying increased transcriptome and proteome complexity. Here, we show that the nuclear speckle RNA-binding protein (NSR) and the AS competitor long noncoding RNA (or ASCO-lncRN...
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Genome-wide association analysis of eosinophilic esophagitis provides insight into the tissue specificity of this allergic disease.
Published: July, 2014

Abstract: Eosinophilic esophagitis (EoE) is a chronic inflammatory disorder associated with allergic hypersensitivity to food. We interrogated >1.5 million genetic variants in EoE cases of European ancestry and subsequently in a multi-site cohort with lo...
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Noncoding Transcription by Alternative RNA Polymerases Dynamically Regulates an Auxin-Driven Chromatin Loop.
Published: July, 2014

Abstract: The eukaryotic epigenome is shaped by the genome topology in three-dimensional space. Dynamic reversible variations in this epigenome structure directly influence the transcriptional responses to developmental cues. Here, we show that the Arabidop...
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Two CCAAT box-binding transcription factors redundantly regulate early steps of the legume-rhizobia endosymbiosis.
Published: June, 2014

Abstract: During endosymbiotic interactions between legume plants and nitrogen-fixing rhizobia, successful root infection by bacteria and nodule organogenesis requires the perception and transduction of bacterial lipo-chitooligosaccharidic signal called Nod...
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Demethylation of the human eotaxin-3 gene promoter leads to the elevated expression of eotaxin-3.
Published: January, 2014

Abstract: DNA demethylation has been primarily studied in the context of development biology, cell fate, and cancer, with less attention on inflammation. In this article, we investigate the association between DNA methylation and production of the chemoattr...
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Histone lysine trimethylation or acetylation can be modulated by phytoestrogen, estrogen or anti-HDAC in breast cancer cell lines.
Published: February, 2013

Abstract: AIM: The isoflavones genistein, daidzein and equol (daidzein metabolite) have been reported to interact with epigenetic modifications, specifically hypermethylation of tumor suppressor genes. The objective of this study was to analyze and understa...
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HMGA1 Reprograms Somatic Cells into Pluripotent Stem Cells by Inducing Stem Cell Transcriptional Networks.
Published: November, 2012

Abstract: BACKGROUND: Although recent studies have identified genes expressed in human embryonic stem cells (hESCs) that induce pluripotency, the molecular underpinnings of normal stem cell function remain poorly understood. The high mobility group A1 (HMGA...
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Genome-Wide Analysis of Methylation in Bovine Clones by Methylated DNA Immunoprecipitation (MeDIP)

Abstract: Methylated DNA immunoprecipitation (MeDIP), when coupled to high-throughput sequencing or microarray hybridization, allows for the identification of methylated loci at a genome-wide scale. Genomic regions affected by incomplete reprogramming after...
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