Epigenetic Mechanisms Mediating Cell State Transitions in Chondrocytes Published: May, 2022 Abstract:
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... Read more »
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 ... Read more »
PPARɣ drives IL-33-dependent ILC2 pro-tumoral functions. Published: May, 2021 Abstract:
Group 2 innate lymphoid cells (ILC2s) play a critical role in protection against helminths and in diverse inflammatory diseases by responding to soluble factors such as the alarmin IL-33, that is often overexpressed in cancer. Nonetheless, regulat... Read more »
The anti-inflammatory cytokine interleukin-37 is an inhibitor of trainedimmunity. Published: April, 2021 Abstract:
Trained immunity (TI) is a de facto innate immune memory program induced in monocytes/macrophages by exposure to pathogens or vaccines, which evolved as protection against infections. TI is characterized by immunometabolic changes and histone post... Read more »
Loss of SETD1B results in the redistribution of genomic H3K4me3 in theoocyte Published: March, 2021 Abstract:
Histone 3 lysine 4 trimethylation (H3K4me3) is an epigenetic mark found at gene promoters and CpG islands. H3K4me3 is essential for mammalian development, yet mechanisms underlying its genomic targeting are poorly understood. H3K4me3 methyltransfe... Read more »
Transgenic mice for in vivo epigenome editing with CRISPR-based systems Published: March, 2021 Abstract:
The discovery, characterization, and adaptation of the RNA-guided clustered regularly interspersed short palindromic repeat (CRISPR)-Cas9 system has greatly increased the ease with which genome and epigenome editing can be performed. Fusion of chr... Read more »
Unique Patterns of H3K4me3 and H3K27me3 in 2-Cell-like Embryonic StemCells. Published: March, 2021 Abstract:
A small subgroup of embryonic stem cells (ESCs) exhibit molecular features similar to those of two-cell embryos (2C). However, it remains elusive whether 2C-like cells and 2C embryos share similar epigenetic features. Here, we map the genome-wide ... Read more »
Epigenomic tensor predicts disease subtypes and reveals constrained tumorevolution. Published: March, 2021 Abstract:
Understanding the epigenomic evolution and specificity of disease subtypes from complex patient data remains a major biomedical problem. We here present DeCET (decomposition and classification of epigenomic tensors), an integrative computational a... Read more »
The histone modification H3K4me3 is altered at the locus in Alzheimer'sdisease brain. Published: February, 2021 Abstract:
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 ... Read more »
REPROGRAMMING CBX8-PRC1 FUNCTION WITH A POSITIVE ALLOSTERICMODULATOR Published: February, 2021 Abstract:
Canonical targeting of Polycomb Repressive Complex 1 (PRC1) to repress developmental genes is mediated by cell type-specific, paralogous chromobox (CBX) proteins (CBX2, 4, 6, 7 and 8). Based on their central role in silencing and their misregulati... Read more »
STAG proteins promote cohesin ring loading at R-loops Published: February, 2021 Abstract:
Most studies of cohesin function consider the Stromalin Antigen (STAG/SA) proteins as core complex members given their ubiquitous interaction with the cohesin ring. Here, we provide functional data to support the notion that the SA subunit is not ... Read more »
The epigenetic landscape in purified myonuclei from fast and slow muscles Published: February, 2021 Abstract:
Muscle cells have different phenotypes adapted to different usage and can be grossly divided into fast/glycolytic and slow/oxidative types. While most muscles contain a mixture of such fiber types, we aimed at providing a genome-wide analysis of c... Read more »
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-... Read more »
Inhibition of HIV-1 gene transcription by KAP1 in myeloid lineage. Published: January, 2021 Abstract:
HIV-1 latency generates reservoirs that prevent viral eradication by the current therapies. To find strategies toward an HIV cure, detailed understandings of the molecular mechanisms underlying establishment and persistence of the reservoirs are n... Read more »
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... Read more »
Dissecting Herpes Simplex Virus 1-Induced Host Shutoff at the RNA Level. Published: November, 2020 Abstract:
Herpes simplex virus 1 (HSV-1) induces a profound host shut-off during lytic infection. The virion host shut-off () protein plays a key role in this process by efficiently cleaving host and viral mRNAs. Furthermore, the onset of viral DNA replicat... Read more »
BCG Vaccination Induces Long-Term Functional Reprogramming of HumanNeutrophils. Published: November, 2020 Abstract:
The tuberculosis vaccine bacillus Calmette-Guérin (BCG) protects against some heterologous infections, probably via induction of non-specific innate immune memory in monocytes and natural killer (NK) cells, a process known as trained immuni... Read more »
ZNF354C is a transcriptional repressor that inhibits endothelialangiogenic sprouting. Published: November, 2020 Abstract:
Zinc finger proteins (ZNF) are a large group of transcription factors with diverse functions. We recently discovered that endothelial cells harbour a specific mechanism to limit the action of ZNF354C, whose function in endothelial cells is unknown... Read more »
p53 directly represses human LINE1 transposons. Published: October, 2020 Abstract:
p53 is a potent tumor suppressor and commonly mutated in human cancers. Recently, we demonstrated that p53 genes act to restrict retrotransposons in germline tissues of flies and fish but whether this activity is conserved in somatic human cells i... Read more »
Between-Generation Phenotypic and Epigenetic Stability in a Clonal Snail. Published: September, 2020 Abstract:
Epigenetic variation might play an important role in generating adaptive phenotypes by underpinning within-generation developmental plasticity, persistent parental effects of the environment (e.g., transgenerational plasticity), or heritable epige... Read more »
OxLDL-mediated immunologic memory in endothelial cells. Published: July, 2020 Abstract:
Trained innate immunity describes the metabolic reprogramming and long-term proinflammatory activation of innate immune cells in response to different pathogen or damage associated molecular patterns, such as oxidized low-density lipoprotein (oxLD... Read more »
The CDK4/6-EZH2 pathway is a potential therapeutic target for psoriasis. Published: July, 2020 Abstract:
Psoriasis is a frequent inflammatory skin disease characterized by keratinocyte hyperproliferation and a disease-related infiltration of immune cells. Here, we identified a novel pro-inflammatory signaling pathway driven by the cyclin-dependent ki... Read more »
MeCP2 regulates gene expression through recognition of H3K27me3. Published: July, 2020 Abstract:
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 sug... Read more »
Premature termination codons in the gene cause reduced local mRNA synthesis. Published: July, 2020 Abstract:
Duchenne muscular dystrophy (DMD) is caused by mutations in the gene leading to the presence of premature termination codons (PTC). Previous transcriptional studies have shown reduced DMD transcript levels in DMD patient and animal model muscles w... Read more »
Identification of Novel Molecular Markers of Human Th17 Cells. Published: July, 2020 Abstract:
Th17 cells are important players in host defense against pathogens such as , , and . Th17 cell-mediated inflammation, under certain conditions in which balance in the immune system is disrupted, is the underlying pathogenic mechanism of certain au... Read more »
Detection of renal cell carcinoma using plasma and urine cell-free DNA methylomes. Published: June, 2020 Abstract:
Improving early cancer detection has the potential to substantially reduce cancer-related mortality. Cell-free methylated DNA immunoprecipitation and high-throughput sequencing (cfMeDIP-seq) is a highly sensitive assay capable of detecting early-s... Read more »
The 20S proteasome activator PA28γ controls the compaction of chromatin Published: May, 2020 Abstract:
The nuclear PA28γ is known to activate the 20S proteasome, but its precise cellular functions remains unclear. Here, we identify PA28γ as a key factor that structures heterochromatin. We find that in human cells, a fraction of PA28&gam... Read more »
Measuring Histone Modifications in the Human Parasite Schistosoma mansoni Published: May, 2020 Abstract:
DNA-binding proteins play critical roles in many major processes such as development and sexual biology of Schistosoma mansoni and are important for the pathogenesis of schistosomiasis. Chromatin immunoprecipitation (ChIP) experiments followed by ... Read more »
AP-1 controls the p11-dependent antidepressant response. Published: May, 2020 Abstract:
Selective serotonin reuptake inhibitors (SSRIs) are the most widely prescribed drugs for mood disorders. While the mechanism of SSRI action is still unknown, SSRIs are thought to exert therapeutic effects by elevating extracellular serotonin level... Read more »
Non-coding somatic mutations converge on the PAX8 pathway in ovarian cancer. Published: April, 2020 Abstract:
The functional consequences of somatic non-coding mutations in ovarian cancer (OC) are unknown. To identify regulatory elements (RE) and genes perturbed by acquired non-coding variants, here we establish epigenomic and transcriptomic landscapes of... Read more »
An epigenetic map of malaria parasite development from host to vector. Published: April, 2020 Abstract:
The malaria parasite replicates asexually in the red blood cells of its vertebrate host employing epigenetic mechanisms to regulate gene expression in response to changes in its environment. We used chromatin immunoprecipitation followed by sequen... Read more »
Abo1 is required for the H3K9me2 to H3K9me3 transition in heterochromatin. Published: April, 2020 Abstract:
Heterochromatin regulation is critical for genomic stability. Different H3K9 methylation states have been discovered, with distinct roles in heterochromatin formation and silencing. However, how the transition from H3K9me2 to H3K9me3 is controlled... Read more »
ChromID identifies the protein interactome at chromatin marks. Published: March, 2020 Abstract:
Chromatin modifications regulate genome function by recruiting proteins to the genome. However, the protein composition at distinct chromatin modifications has yet to be fully characterized. In this study, we used natural protein domains as modula... Read more »
HDAC3 functions as a positive regulator in Notch signal transduction. Published: February, 2020 Abstract:
Aberrant Notch signaling plays a pivotal role in T-cell acute lymphoblastic leukemia (T-ALL) and chronic lymphocytic leukemia (CLL). Amplitude and duration of the Notch response is controlled by ubiquitin-dependent proteasomal degradation of the N... Read more »
DNA Methylation Editing by CRISPR-guided Excision of 5-Methylcytosine. Published: February, 2020 Abstract:
Tools for actively targeted DNA demethylation are required to increase our knowledge about regulation and specific functions of this important epigenetic modification. DNA demethylation in mammals involves TET-mediated oxidation of 5-methylcytosin... Read more »
miR-155 inhibits mitophagy through suppression of BAG5, a partner protein of PINK1. Published: January, 2020 Abstract:
Removal of dysfunctional mitochondria is essential step to maintain normal cell physiology, and selective autophagy in mitochondria, called mitophagy, plays a critical role in quality control of mitochondria. While in several diseases and aging, d... Read more »
H3K4me1 Supports Memory-like NK Cells Induced by Systemic Inflammation. Published: December, 2019 Abstract:
Natural killer (NK) cells are unique players in innate immunity and, as such, an attractive target for immunotherapy. NK cells display immune memory properties in certain models, but the long-term status of NK cells following systemic inflammation... Read more »
Trained immunity modulates inflammation-induced fibrosis. Published: December, 2019 Abstract:
Chronic inflammation and fibrosis can result from inappropriately activated immune responses that are mediated by macrophages. Macrophages can acquire memory-like characteristics in response to antigen exposure. Here, we show the effect of BCG or ... Read more »
MicroRNA-708 is a novel regulator of the Hoxa9 program in myeloid cells. Published: November, 2019 Abstract:
MicroRNAs (miRNAs) are commonly deregulated in acute myeloid leukemia (AML), affecting critical genes not only through direct targeting, but also through modulation of downstream effectors. Homeobox (Hox) genes balance self-renewal, proliferation,... Read more »
R-Loops Promote Antisense Transcription across the Mammalian Genome Published: November, 2019 Abstract:
Widespread antisense long noncoding RNA (lncRNA) overlap with many protein-coding genes in mammals and emanate from gene promoter, enhancer, and termination regions. However, their origin and biological purpose remain unclear. We show that these a... Read more »
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... Read more »
TET2 Regulates the Neuroinflammatory Response in Microglia. Published: October, 2019 Abstract:
Epigenomic mechanisms regulate distinct aspects of the inflammatory response in immune cells. Despite the central role for microglia in neuroinflammation and neurodegeneration, little is known about their epigenomic regulation of the inflammatory ... Read more »
Assaying epigenome functions of PRMTs and their substrates. Published: September, 2019 Abstract:
Among the widespread and increasing number of identified post-translational modifications (PTMs), arginine methylation is catalyzed by the protein arginine methyltransferases (PRMTs) and regulates fundamental processes in cells, such as gene regul... Read more »
Relationship between osteoporosis and osteoarthritis based on DNA methylation Published: September, 2019 Abstract:
: The aim of this study was to investigate the relationship between osteoporosis and osteoarthritis by analyzing the DNA methylation in osteoporosis and osteoarthritis. The cancellous bone specimens were collected from a total of 12 hospitalized p... Read more »
Improved double-nicking strategies for COL7A1 editing by homologous recombination Published: September, 2019 Abstract:
Current gene editing approaches for treatment of recessive dystrophic epidermolysis bullosa (RDEB), an inherited, severe form of blistering skin disease, suffer from low efficiencies and safety concerns that complicate implementation in clinical s... Read more »
Improved Double-Nicking Strategies for COL7A1-Editing by Homologous Recombination. Published: September, 2019 Abstract:
Current gene-editing approaches for treatment of recessive dystrophic epidermolysis bullosa (RDEB), an inherited, severe form of blistering skin disease, suffer from low efficiencies and safety concerns that complicate implementation in clinical s... Read more »
Nucleome Dynamics during Retinal Development. Published: August, 2019 Abstract:
More than 8,000 genes are turned on or off as progenitor cells produce the 7 classes of retinal cell types during development. Thousands of enhancers are also active in the developing retinae, many having features of cell- and developmental stage-... Read more »
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... Read more »
Acetate Promotes T Cell Effector Function during Glucose Restriction. Published: May, 2019 Abstract:
Competition for nutrients like glucose can metabolically restrict T cells and contribute to their hyporesponsiveness during cancer. Metabolic adaptation to the surrounding microenvironment is therefore key for maintaining appropriate cell fun... Read more »
ARv7 Represses Tumor-Suppressor Genes in Castration-Resistant Prostate Cancer. Published: March, 2019 Abstract:
Androgen deprivation therapy for prostate cancer (PCa) benefits patients with early disease, but becomes ineffective as PCa progresses to a castration-resistant state (CRPC). Initially CRPC remains dependent on androgen receptor (AR) signaling, of... Read more »
The role of TCF3 as potential master regulator in blastemal Wilms tumors. Published: March, 2019 Abstract:
Wilms tumors are the most common type of pediatric kidney tumors. While the overall prognosis for patients is favorable, especially tumors that exhibit a blastemal subtype after preoperative chemotherapy have a poor prognosis. For an improved risk... Read more »
R-Loops Enhance Polycomb Repression at a Subset of Developmental Regulator Genes. Published: March, 2019 Abstract:
R-loops are three-stranded nucleic acid structures that form during transcription, especially over unmethylated CpG-rich promoters of active genes. In mouse embryonic stem cells (mESCs), CpG-rich developmental regulator genes are repressed by the ... Read more »
The Wnt-Driven Mll1 Epigenome Regulates Salivary Gland and Head and Neck Cancer. Published: January, 2019 Abstract:
We identified a regulatory system that acts downstream of Wnt/β-catenin signaling in salivary gland and head and neck carcinomas. We show in a mouse tumor model of K14-Cre-induced Wnt/β-catenin gain-of-function and Bmpr1a loss-of-functio... Read more »
Identification of ChIP-seq and RIME grade antibodies for Estrogen Receptor alpha. Published: January, 2019 Abstract:
Estrogen Receptor alpha (ERα) plays a major role in most breast cancers, and it is the target of endocrine therapies used in the clinic as standard of care for women with breast cancer expressing this receptor. The two methods ChIP-seq (chro... Read more »
Mutant p63 Affects Epidermal Cell Identity through Rewiring the Enhancer Landscape. Published: December, 2018 Abstract:
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, ... Read more »
Enhancers in the Peril lincRNA locus regulate distant but not local genes. Published: December, 2018 Abstract:
BACKGROUND: Recently, it has become clear that some promoters function as long-range regulators of gene expression. However, direct and quantitative assessment of enhancer activity at long intergenic noncoding RNA (lincRNA) or mRNA gene bodies has... Read more »
Can Mitochondrial DNA be CRISPRized: Pro and Contra. Published: December, 2018 Abstract:
Mitochondria represent a chimera of macromolecules encoded either in the organellar genome, mtDNA, or in the nuclear one. If the pathway of protein targeting to different sub-compartments of mitochondria was relatively well studied, import of smal... Read more »
Genomic integrity of ground-state pluripotency. Published: December, 2018 Abstract:
Pluripotent cells appear to be in a transient state during early development. These cells have the capability to transition into embryonic stem cells (ESCs). It has been reported that mouse pluripotent cells cultivated in chemically defined media ... Read more »
Sensitive tumour detection and classification using plasma cell-free DNA methylomes. Published: November, 2018 Abstract:
The use of liquid biopsies for cancer detection and management is rapidly gaining prominence. Current methods for the detection of circulating tumour DNA involve sequencing somatic mutations using cell-free DNA, but the sensitivity of these method... Read more »
TET2 inhibits tumorigenesis of breast cancer cells by regulating caspase-4. Published: November, 2018 Abstract:
Epigenetic regulators have been shown to influence breast cancer progression. However, the detailed mechanism by which TET2 plays the suppressive role in tumorigenesis remains not completely understood. We employed RT-qPCR and westernblot to exami... Read more »
TRPS1 Is a Lineage-Specific Transcriptional Dependency in Breast Cancer. Published: October, 2018 Abstract:
Perturbed epigenomic programs play key roles in tumorigenesis, and chromatin modulators are candidate therapeutic targets in various human cancer types. To define singular and shared dependencies on DNA and histone modifiers and transcription fact... Read more »
Centromeres License the Mitotic Condensation of Yeast Chromosome Arms. Published: October, 2018 Abstract:
During mitosis, chromatin condensation shapes chromosomes as separate, rigid, and compact sister chromatids to facilitate their segregation. Here, we show that, unlike wild-type yeast chromosomes, non-chromosomal DNA circles and chromosomes lackin... Read more »
Promoter bivalency favors an open chromatin architecture in embryonic stem cells. Published: October, 2018 Abstract:
In embryonic stem cells (ESCs), developmental gene promoters are characterized by their bivalent chromatin state, with simultaneous modification by MLL2 and Polycomb complexes. Although essential for embryogenesis, bivalency is functionally not we... Read more »
Transcription Elongation Can Affect Genome 3D Structure. Published: September, 2018 Abstract:
How transcription affects genome 3D organization is not well understood. We found that during influenza A (IAV) infection, rampant transcription rapidly reorganizes host cell chromatin interactions. These changes occur at the ends of highly transc... Read more »
HIV-2/SIV viral protein X counteracts HUSH repressor complex. Published: August, 2018 Abstract:
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 antagoniz... Read more »
The transcriptional factor ZEB1 represses Syndecan 1 expression in prostate cancer. Published: July, 2018 Abstract:
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 transit... Read more »
MTF2 recruits Polycomb Repressive Complex 2 by helical-shape-selective DNA binding. Published: July, 2018 Abstract:
ABSTACT: Polycomb-mediated repression of gene expression is essential for development, with a pivotal role played by trimethylation of histone H3 lysine 27 (H3K27me3), which is deposited by Polycomb Repressive Complex 2 (PRC2). The mechanism by wh... Read more »
TSPYL2 Regulates the Expression of EZH2 Target Genes in Neurons Published: July, 2018 Abstract:
Testis-specific protein, Y-encoded-like 2 (TSPYL2) is an X-linked gene in the locus for several neurodevelopmental disorders. We have previously shown that Tspyl2 knockout mice had impaired learning and sensorimotor gating, and TSPYL2 facilitates ... Read more »
Integrative multi-omics analysis of intestinal organoid differentiation Published: June, 2018 Abstract:
Intestinal organoids accurately recapitulate epithelial homeostasis in vivo, thereby representing a powerful in vitro system to investigate lineage specification and cellular differentiation. Here, we applied a multi-omics framework on stem cell-e... Read more »
Epigenetic inheritance mediated by coupling of RNAi and histone H3K9 methylation. Published: June, 2018 Abstract:
Histone post-translational modifications (PTMs) are associated with epigenetic states that form the basis for cell-type-specific gene expression. Once established, histone PTMs can be maintained by positive feedback involving enzymes that recogniz... Read more »
Modulation of vitamin D signaling by the pioneer factor CEBPA. Published: June, 2018 Abstract:
The myeloid master regulator CCAAT enhancer-binding protein alpha (CEBPA) is known as a pioneer factor. In this study, we report the CEBPA cistrome of THP-1 human monocytes after stimulation with the vitamin D receptor (VDR) ligand 1α,25-dih... Read more »
Determination of the presence of 5-methylcytosine in Paramecium tetraurelia. Published: June, 2018 Abstract:
5-methylcytosine DNA methylation regulates gene expression and developmental programming in a broad range of eukaryotes. However, its presence and potential roles in ciliates, complex single-celled eukaryotes with germline-somatic genome specializ... Read more »
Immunity drives regulation in cancer through NF-κB. Published: June, 2018 Abstract:
Ten-eleven translocation enzymes (TET1, TET2, and TET3), which induce DNA demethylation and gene regulation by converting 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), are often down-regulated in cancer. We uncover, in basal-like breas... Read more »
Immunity drives TET1 regulation in cancer through NF-kB Published: June, 2018 Abstract:
Ten-eleven translocation enzymes (TET1, TET2, and TET3), which induce DNA demethylation and gene regulation by converting 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), are often down-regulated in cancer. We uncover, in basal-like breas... Read more »
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 ... Read more »
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... Read more »
Comparative Analysis of Immune Cells Reveals a Conserved Regulatory Lexicon. Published: March, 2018 Abstract:
Most well-characterized enhancers are deeply conserved. In contrast, genome-wide comparative studies of steady-state systems showed that only a small fraction of active enhancers are conserved. To better understand conservation of enhancer activit... Read more »
Genome-wide analysis of PDX1 target genes in human pancreatic progenitors. Published: March, 2018 Abstract:
OBJECTIVE: Homozygous loss-of-function mutations in the gene coding for the homeobox transcription factor (TF) PDX1 leads to pancreatic agenesis, whereas heterozygous mutations can cause Maturity-Onset Diabetes of the Young 4 (MODY4). Although the... Read more »
A Non-catalytic Function of SETD1A Regulates Cyclin K and the DNA Damage Response. Published: February, 2018 Abstract:
MLL/SET methyltransferases catalyze methylation of histone 3 lysine 4 and play critical roles in development and cancer. We assessed MLL/SET proteins and found that SETD1A is required for survival of acute myeloid leukemia (AML) cells. Mutagenesis... Read more »
Metabolic Induction of Trained Immunity through the Mevalonate Pathway. Published: January, 2018 Abstract:
Innate immune cells can develop long-term memory after stimulation by microbial products during infections or vaccinations. Here, we report that metabolic signals can induce trained immunity. Pharmacological and genetic experiments reveal that act... Read more »
Senescence-associated reprogramming promotes cancer stemness. Published: January, 2018 Abstract:
Cellular senescence is a stress-responsive cell-cycle arrest program that terminates the further expansion of (pre-)malignant cells. Key signalling components of the senescence machinery, such as p16, p21 and p53, as well as trimethylation of lysi... Read more »
STAT5BN642H is a driver mutation for T cell neoplasia Published: January, 2018 Abstract:
STAT5B is often mutated in hematopoietic malignancies. The most frequent STAT5B mutation, Asp642His (N642H), has been found in over 90 leukemia and lymphoma patients. Here, we used the Vav1 promoter to generate transgenic mouse models that express... Read more »
Genome-wide analysis of day/night DNA methylation differences in Populus nigra. Published: January, 2018 Abstract:
DNA methylation is an important mechanism of epigenetic modification. Methylation changes during stress responses and developmental processes have been well studied; however, their role in plant adaptation to the day/night cycle is poorly understo... Read more »
MLL2 conveys transcription-independent H3K4 trimethylation in oocytes Published: January, 2018 Abstract:
Histone 3 K4 trimethylation (depositing H3K4me3 marks) is typically associated with active promoters yet paradoxically occurs at untranscribed domains. Research to delineate the mechanisms of targeting H3K4 methyltransferases is ongoing. The oocyt... Read more »
BRACHYURY directs histone acetylation to target loci during mesoderm development. Published: January, 2018 Abstract:
T-box transcription factors play essential roles in multiple aspects of vertebrate development. Here, we show that cooperative function of BRACHYURY (T) with histone-modifying enzymes is essential for mouse embryogenesis. A single point mutation (... Read more »
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... Read more »
5-Methylcytosine RNA Methylation in Arabidopsis Thaliana Published: November, 2017 Abstract:
5-Methylcytosine (m5C) is a well-characterized DNA modification, and is also predominantly reported in abundant non-coding RNAs in both prokaryotes and eukaryotes. However, the distribution and biological functions of m5C in plant mRNAs remain lar... Read more »
CDK8/19 Mediator kinases potentiate induction of transcription by NFκB Published: September, 2017 Abstract:
The nuclear factor-κB (NFκB) family of transcription factors has been implicated in inflammatory disorders, viral infections, and cancer. Most of the drugs that inhibit NFκB show significant side effects, possibly due to sustaine... Read more »
Distinct Circadian Signatures in Liver and Gut Clocks Revealed by Ketogenic Diet Published: September, 2017 Abstract:
The circadian clock orchestrates rhythms in physiology and behavior, allowing organismal adaptation to daily environmental changes. While food intake profoundly influences diurnal rhythms in the liver, how nutritional challenges are differentially... Read more »
Epigenetic variation between urban and rural populations of Darwin's finches Published: August, 2017 Abstract:
Background
The molecular basis of evolutionary change is assumed to be genetic variation. However, growing evidence suggests that epigenetic mechanisms, such as DNA methylation, may also be involved in rapid adaptation to new environments. An... Read more »
Highly efficient gene inactivation by adenoviral CRISPR/Cas9 in human primary cells Published: August, 2017 Abstract:
Phenotypic assays using human primary cells are highly valuable tools for target discovery and validation in drug discovery. Expression knockdown (KD) of such targets in these assays allows the investigation of their role in models of disease proc... Read more »
Circadian Reprogramming in the Liver Identifies Metabolic Pathways of Aging Published: August, 2017 Abstract:
The process of aging and circadian rhythms are intimately intertwined, but how peripheral clocks involved in metabolic homeostasis contribute to aging remains unknown. Importantly, caloric restriction (CR) extends lifespan in several organisms and... Read more »
Chromatin Immunoprecipitation (ChIP) in Mouse T-cell Lines Published: June, 2017 Abstract:
Signaling pathways regulate gene expression programs via the modulation of the chromatin structure at different levels, such as by post-translational modifications (PTMs) of histone tails, the exchange of canonical histones with histone variants, ... Read more »
HDAC1 links early life stress to schizophrenia-like phenotypes Published: June, 2017 Abstract:
Schizophrenia is a devastating disease that arises on the background of genetic predisposition and environmental risk factors, such as early life stress (ELS). In this study, we show that ELS-induced schizophrenia-like phenotypes in mice correlate... Read more »
Characterization of the Polycomb-Group Mark H3K27me3 in Unicellular Algae Published: April, 2017 Abstract:
Polycomb Group (PcG) proteins mediate chromatin repression in plants and animals by catalyzing H3K27 methylation and H2AK118/119 mono-ubiquitination through the activity of the Polycomb repressive complex 2 (PRC2) and PRC1, respectively. PcG prote... Read more »
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... Read more »
Connexin43 controls N-cadherin transcription during collective cell migration Published: March, 2017 Abstract:
Connexins are the primary components of gap junctions, providing direct links between cells in many physiological processes, including cell migration and cancer metastasis. Exactly how cell migration is controlled by gap junctions remains a myster... Read more »
Assessing histone demethylase inhibitors in cells: lessons learned Published: March, 2017 Abstract:
Background
Histone lysine demethylases (KDMs) are of interest as drug targets due to their regulatory roles in chromatin organization and their tight associations with diseases including cancer and mental disorders. The first KDM inhibitors for... Read more »
RNF40 regulates gene expression in an epigenetic context-dependent manner Published: February, 2017 Abstract:
BACKGROUND:
Monoubiquitination of H2B (H2Bub1) is a largely enigmatic histone modification that has been linked to transcriptional elongation. Because of this association, it has been commonly assumed that H2Bub1 is an exclusively positively ac... Read more »
A novel DLX3-PKC integrated signaling network drives keratinocyte differentiation Published: February, 2017 Abstract:
Epidermal homeostasis relies on a well-defined transcriptional control of keratinocyte proliferation and differentiation, which is critical to prevent skin diseases such as atopic dermatitis, psoriasis or cancer. We have recently shown that the ho... Read more »
DNA methylation heterogeneity defines a disease spectrum in Ewing sarcoma Published: January, 2017 Abstract:
Developmental tumors in children and young adults carry few genetic alterations, yet they have diverse clinical presentation. Focusing on Ewing sarcoma, we sought to establish the prevalence and characteristics of epigenetic heterogeneity in genet... Read more »
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... Read more »
Immunometabolic Pathways in BCG-Induced Trained Immunity Published: December, 2016 Abstract:
The protective effects of the tuberculosis vaccine Bacillus Calmette-Guerin (BCG) on unrelated infections are thought to be mediated by long-term metabolic changes and chromatin remodeling through histone modifications in innate immune cells such ... Read more »
A transcription factor pulse can prime chromatin for heritable transcriptional memory Published: December, 2016 Abstract:
Short-term and long-term transcriptional memory is the phenomenon whereby the kinetics or magnitude of gene induction is enhanced following a prior induction period. Short-term memory persists within one cell generation or in post-mitotic cells, w... Read more »
Potent and selective bivalent inhibitors of BET bromodomains Published: December, 2016 Abstract:
Proteins of the bromodomain and extraterminal (BET) family, in particular bromodomain-containing protein 4 (BRD4), are of great interest as biological targets. BET proteins contain two separate bromodomains, and existing inhibitors bind to them mo... Read more »
TET-dependent regulation of retrotransposable elements in mouse embryonic stem cells Published: November, 2016 Abstract:
BACKGROUND:
Ten-eleven translocation (TET) enzymes oxidise DNA methylation as part of an active demethylation pathway. Despite extensive research into the role of TETs in genome regulation, little is known about their effect on transposable ele... Read more »
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... Read more »
β-Glucan Reverses the Epigenetic State of LPS-Induced Immunological Tolerance Published: November, 2016 Abstract:
Innate immune memory is the phenomenon whereby innate immune cells such as monocytes or macrophages undergo functional reprogramming after exposure to microbial components such as lipopolysaccharide (LPS). We apply an integrated epigenomic ap... Read more »
EPOP Functionally Links Elongin and Polycomb in Pluripotent Stem Cells Published: November, 2016 Abstract:
The cellular plasticity of pluripotent stem cells is thought to be sustained by genomic regions that display both active and repressive chromatin properties. These regions exhibit low levels of gene expression, yet the mechanisms controlling these... Read more »
Reader domain specificity and lysine demethylase-4 family function Published: November, 2016 Abstract:
The KDM4 histone demethylases are conserved epigenetic regulators linked to development, spermatogenesis and tumorigenesis. However, how the KDM4 family targets specific chromatin regions is largely unknown. Here, an extensive histone peptide micr... Read more »
TET2 binds the androgen receptor and loss is associated with prostate cancer Published: November, 2016 Abstract:
Genetic alterations associated with prostate cancer (PCa) may be identified by sequencing metastatic tumour genomes to identify molecular markers at this lethal stage of disease. Previously, we characterized somatic alterations in metastatic tumou... Read more »
Chromatin Preparation and Chromatin Immuno-precipitation from Drosophila Embryos Published: November, 2016 Abstract:
This protocol provides specific details on how to perform Chromatin immunoprecipitation (ChIP) from Drosophila embryos. ChIP allows the matching of proteins or histone modifications to specific genomic regions. Formaldehyde-cross-linked chromatin ... Read more »
Neonatal monocytes exhibit a unique histone modification landscape Published: September, 2016 Abstract:
Background
Neonates have dampened expression of pro-inflammatory cytokines and difficulty clearing pathogens. This makes them uniquely susceptible to infections, but the factors regulating neonatal-specific immune responses are poorly understoo... Read more »
Heterochromatic histone modifications at transposons in Xenopus tropicalis embryos Published: September, 2016 Abstract:
Transposable elements are parasitic genomic elements that can be deleterious for host gene function and genome integrity. Heterochromatic histone modifications are involved in the repression of transposons. However, it remains unknown how these hi... Read more »
Fumarate is an epigenetic modifier that elicits epithelial-to-mesenchymal transition Published: August, 2016 Abstract:
Mutations of the tricarboxylic acid cycle enzyme fumarate hydratase cause hereditary leiomyomatosis and renal cell cancer1. Fumarate hydratase-deficient renal cancers are highly aggressive and metastasize even when small, leading to a very poor cl... Read more »
MEF2C protects bone marrow B-lymphoid progenitors during stress haematopoiesis Published: August, 2016 Abstract:
DNA double strand break (DSB) repair is critical for generation of B-cell receptors, which are pre-requisite for B-cell progenitor survival. However, the transcription factors that promote DSB repair in B cells are not known. Here we show that MEF... Read more »
Severe muscle wasting and denervation in mice lacking the RNA-binding protein ZFP106 Published: August, 2016 Abstract:
Innervation of skeletal muscle by motor neurons occurs through the neuromuscular junction, a cholinergic synapse essential for normal muscle growth and function. Defects in nerve-muscle signaling cause a variety of neuromuscular disorders with fea... Read more »
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... Read more »
Osr1 Interacts Synergistically with Wt1 to Regulate Kidney Organogenesis Published: July, 2016 Abstract:
Renal hypoplasia is a common cause of pediatric renal failure and several adult-onset diseases. Recent studies have associated a variant of the OSR1 gene with reduction of newborn kidney size and function in heterozygotes and neonatal lethality wi... Read more »
MEIS2 Is an Oncogenic Partner in AML1-ETO-Positive AML Published: July, 2016 Abstract:
Homeobox genes are known to be key factors in leukemogenesis. Although the TALE family homeodomain factor Meis1 has been linked to malignancy, a role for MEIS2 is less clear. Here, we demonstrate that MEIS2 is expressed at high levels in patients ... Read more »
Epigenetic silencing of serine protease HTRA1 drives polyploidy Published: July, 2016 Abstract:
BACKGROUND:
Increased numbers and improperly positioned centrosomes, aneuploidy or polyploidy, and chromosomal instability are frequently observed characteristics of cancer cells. While some aspects of these events and the checkpoint mechanisms... Read more »
PHF13 is a molecular reader and transcriptional co-regulator of H3K4me2/3 Published: May, 2016 Abstract:
PHF13 is a chromatin affiliated protein with a functional role in differentiation, cell division, DNA damage response and higher chromatin order. To gain insight into PHF13's ability to modulate these processes, we elucidate the mechanisms targeti... Read more »
Three Novel Heterozygous Point Mutations of NR3C1 causing Glucocorticoid Resistance Published: April, 2016 Abstract:
Generalized glucocorticoid resistance is associated with glucocorticoid receptor (GR, NR3C1) mutations. Three novel heterozygous missense NR3C1 mutations (R477S, Y478C and L672P) were identified in patients presenting with adrenal incidentalomas, ... Read more »
Frequency and mitotic heritability of epimutations in Schistosoma mansoni Published: April, 2016 Abstract:
Schistosoma mansoni is a parasitic platyhelminth responsible for intestinal bilharzia. It has a complex life cycle, infecting a freshwater snail of the Biomphalaria genus, and then a mammalian host. Schistosoma mansoni adapts rapidly to new (allop... Read more »
Sequence features accurately predict genome-wide MeCP2 binding in vivo Published: March, 2016 Abstract:
Methyl-CpG binding protein 2 (MeCP2) is critical for proper brain development and expressed at near-histone levels in neurons, but the mechanism of its genomic localization remains poorly understood. Using high-resolution MeCP2-binding data, we sh... Read more »
Zbtb20 promotes astrocytogenesis during neocortical development Published: March, 2016 Abstract:
Multipotent neural precursor cells (NPCs) generate astrocytes at late stages of mammalian neocortical development. Many signalling pathways that regulate astrocytogenesis directly induce the expression of GFAP, a marker of terminally differentiate... Read more »
Role of Annexin gene and its regulation during zebrafish caudal fin regeneration Published: March, 2016 Abstract:
The molecular mechanism of epimorphic regeneration is elusive due to its complexity and limitation in mammals. Epigenetic regulatory mechanisms play a crucial role in development and regeneration. This investigation attempted to reveal the role of... Read more »
Hydroxymethylation of microRNA-365-3p Regulates Nociceptive Behaviors via Kcnh2 Published: March, 2016 Abstract:
DNA 5-hydroxylmethylcytosine (5hmC) catalyzed by ten-eleven translocation methylcytosine dioxygenase (TET) occurs abundantly in neurons of mammals. However, the in vivo causal link between TET dysregulation and nociceptive modulation has not been ... Read more »
Methylated DNA Immunoprecipitation Analysis of Mammalian Endogenous Retroviruses. Published: February, 2016 Abstract:
Endogenous retroviruses are repetitive sequences found abundantly in mammalian genomes which are capable of modulating host gene expression. Nevertheless, most endogenous retrovirus copies are under tight epigenetic control via histone-repressive ... Read more »
Chemical Biology Approaches for Characterization of Epigenetic Regulators Published: February, 2016 Abstract:
Chemical biology approaches are a powerful means to functionally characterize epigenetic regulators such as histone modifying enzymes. We outline experimental protocols and best practices for the cellular characterization and use of “chemica... Read more »
Expression of the MOZ-TIF2 oncoprotein in mice represses senescence. Published: February, 2016 Abstract:
The MOZ-TIF2 translocation, that fuses MOZ (Monocytic Leukemia Zinc finger protein) histone acetyltransferase (HAT) with the nuclear co-activator TIF2, is associated the development of Acute Myeloid Leukemia. We recently showed that in t... Read more »
Role of Growth Arrest and DNA Damage-Inducible, Beta in Alcohol-Drinking Behaviors Published: February, 2016 Abstract:
BACKGROUND:
The contribution of epigenetic factors, such as histone acetylation and DNA methylation, to the regulation of alcohol-drinking behavior has been increasingly recognized over the last several years. GADD45b is a protein demonstrated to... Read more »
Protocol for Methylated DNA Immunoprecipitation (MeDIP) Analysis Published: February, 2016 Abstract:
DNA methylation is a fundamental epigenetic mechanism for silencing gene expression by either modifying chromatin structure to a repressive state or interfering with the transcription factors’ binding. DNA methylation primarily occurs at the... Read more »
Transcriptome-wide distribution and function of RNA hydroxymethylcytosine Published: January, 2016 Abstract:
Hydroxymethylcytosine, well described in DNA, occurs also in RNA. Here, we show that hydroxymethylcytosine preferentially marks polyadenylated RNAs and is deposited by Tet in Drosophila. We map the transcriptome-wide hydroxymethylation landscape, ... Read more »
De novo DNA methylation drives 5hmC accumulation in mouse zygotes Published: January, 2016 Abstract:
Zygotic epigenetic reprogramming entails genome-wide DNA demethylation that is accompanied by Tet methylcytosine dioxygenase 3 (Tet3)-driven oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC; refs ,,,). Here we demonstrate ... Read more »
Functional characterization of the hGRαT556I causing Chrousos syndrome Published: January, 2016 Abstract:
BACKGROUND:
Chrousos syndrome is a rare pathologic condition characterized by generalized, partial resistance of target tissues to glucocorticoids and caused by inactivating mutations of the human glucocorticoid receptor (hGR) gene. A novel case ... Read more »
cChIP-seq: a robust small-scale method for investigation of histone modifications Published: December, 2015 Abstract:
Background
ChIP-seq is highly utilized for mapping histone modifications that are informative about gene regulation and genome annotations. For example, applying ChIP-seq to histone modifications such as H3K4me1 has facilitated generating epige... Read more »
Embryonic transcription is controlled by maternally defined chromatin state Published: December, 2015 Abstract:
Histone-modifying enzymes are required for cell identity and lineage commitment, however little is known about the regulatory origins of the epigenome during embryonic development. Here we generate a comprehensive set of epigenome reference maps, ... Read more »
Oxidative DNA damage in mouse sperm chromosomes: Size matters. Published: December, 2015 Abstract:
Normal embryo and foetal development as well as the health of the progeny are mostly dependent on gamete nuclear integrity. In the present study, in order to characterize more precisely oxidative DNA damage in mouse sperm we used two mouse models ... Read more »
Transient generalized glucocorticoid hypersensitivity Published: December, 2015 Abstract:
BACKGROUND:
Transient generalized glucocorticoid hypersensitivity is a rare disorder characterized by increased tissue sensitivity to glucocorticoids and compensatory hypo-activation of the hypothalamic-pituitary-adrenal axis. The condition itsel... Read more »
Dynamic changes in histone modifications precede de novo DNA methylation in oocytes Published: December, 2015 Abstract:
Erasure and subsequent reinstatement of DNA methylation in the germline, especially at imprinted CpG islands (CGIs), is crucial to embryogenesis in mammals. The mechanisms underlying DNA methylation establishment remain poorly understood, but a nu... Read more »
CRISPR-Mediated Gene Targeting of Human Induced Pluripotent Stem Cells Published: November, 2015 Abstract:
CRISPR/Cas9 nuclease systems can create double-stranded DNA breaks at specific sequences to efficiently and precisely disrupt, excise, mutate, insert, or replace genes. However, human embryonic stem cells and induced pluripotent stem cells (iPSCs)... Read more »
Optimized method for methylated DNA immuno-precipitation Published: October, 2015 Abstract:
Methylated DNA immunoprecipitation (MeDIP) is one of the most widely used methods to evaluate DNA methylation on a whole genome scale, and involves the capture of the methylated fraction of the DNA by an antibody specific to methyl-cytosine. MeDIP... Read more »
Arabidopsis CMT3 activity is positively regulated by AtSIZ1-mediated sumoylation Published: October, 2015 Abstract:
The activities of mammalian DNA and histone methyltransferases are regulated by post-translational modifications such as phosphorylation and sumoylation; however, it is unclear how the activities of these enzymes are regulated at the post-translat... Read more »
Genome-wide p63-regulated gene expression in differentiating epidermal keratinocytes Published: September, 2015 Abstract:
The transcription factor p63 is a key regulator in epidermal keratinocyte proliferation and differentiation. However, the role of p63 in gene regulation during these processes is not well understood. To investigate this, we recently generated geno... Read more »
Chromatin assembly factor CAF-1 represses priming of plant defence response genes Published: September, 2015 Abstract:
Plants have evolved efficient defence systems against pathogens that often rely on specific transcriptional responses. Priming is part of the defence syndrome, by establishing a hypersensitive state of defence genes such as after a first encounter... Read more »
Rapid and highly efficient mammalian cell engineering via Cas9 protein transfection. Published: August, 2015 Abstract:
CRISPR-Cas9 systems provide a platform for high efficiency genome editing that are enabling innovative applications of mammalian cell engineering. However, the delivery of Cas9 and synthesis of guide RNA (gRNA) remain as steps that can limit overa... Read more »
Genome-wide hydroxymethylcytosine pattern changes in response to oxidative stress Published: August, 2015 Abstract:
The TET enzymes convert methylcytosine to the newly discovered base hydroxymethylcytosine. While recent reports suggest that TETs may play a role in response to oxidative stress, this role remains uncertain, and results lack in vivo models. Here... Read more »
Non-coding recurrent mutations in chronic lymphocytic leukaemia. Published: July, 2015 Abstract:
Chronic lymphocytic leukaemia (CLL) is a frequent disease in which the genetic alterations determining the clinicobiological behaviour are not fully understood. Here we describe a comprehensive evaluation of the genomic landscape of 452 CLL cases ... Read more »
DNA methylation directs functional maturation of pancreatic β cells Published: July, 2015 Abstract:
Pancreatic β cells secrete insulin in response to postprandial increases in glucose levels to prevent hyperglycemia and inhibit insulin secretion under fasting conditions to protect against hypoglycemia. β cells lack this functional capa... Read more »
Gadd45b and N-methyl-D-aspartate induced DNA demethylation in postmitotic neurons. Published: June, 2015 Abstract:
AIM: In nondividing neurons examine the role of Gadd45b in active 5-methylcytosine (5MC) and 5-hydroxymethylcytosine (5HMC) removal at a gene promoter highly implicated in mental illnesses and cognition, Bdnf.
MATERIALS & METHODS: Mouse prima... Read more »
Citrate modulates lipopolysaccharide-induced monocyte inflammatory responses. Published: June, 2015 Abstract:
Citrate, a central component of cellular metabolism, is a widely used anti-coagulant due to its ability to chelate calcium. Adenosine triphosphate (ATP)-citrate lyase, which metabolizes citrate, has been shown to be essential for inflammation, but... Read more »
Targeted disruption of DNMT1, DNMT3A and DNMT3B in human embryonic stem cells. Published: May, 2015 Abstract:
DNA methylation is a key epigenetic modification involved in regulating gene expression and maintaining genomic integrity. Here we inactivated all three catalytically active DNA methyltransferases (DNMTs) in human embryonic stem cells (ESCs) using... Read more »
A cohesin-OCT4 complex mediates Sox enhancers to prime an early embryonic lineage. Published: April, 2015 Abstract:
Short- and long-scales intra- and inter-chromosomal interactions are linked to gene transcription, but the molecular events underlying these structures and how they affect cell fate decision during embryonic development are poorly understood. One ... Read more »
NAD(+)-SIRT1 control of H3K4 trimethylation through circadian deacetylation of MLL1. Published: April, 2015 Abstract:
The circadian clock controls the transcription of hundreds of genes through specific chromatin-remodeling events. The histone methyltransferase mixed-lineage leukemia 1 (MLL1) coordinates recruitment of CLOCK-BMAL1 activator complexes to chromatin... Read more »
Genome-wide CRISPR screen in a mouse model of tumor growth and metastasis. Published: March, 2015 Abstract:
Genetic screens are powerful tools for identifying genes responsible for diverse phenotypes. Here we describe a genome-wide CRISPR/Cas9-mediated loss-of-function screen in tumor growth and metastasis. We mutagenized a non-metastatic mouse cancer c... Read more »
Stable X Chromosome Reactivation in Female Human Induced Pluripotent Stem Cells. Published: January, 2015 Abstract:
In placental mammals, balanced expression of X-linked genes is accomplished by X chromosome inactivation (XCI) in female cells. In humans, random XCI is initiated early during embryonic development. To investigate whether reprogramming of female h... Read more »
Embryonic stem cell differentiation requires full length Chd1. Published: January, 2015 Abstract:
The modulation of chromatin dynamics by ATP-dependent chromatin remodeling factors has been recognized as an important mechanism to regulate the balancing of self-renewal and pluripotency in embryonic stem cells (ESCs). Here we have studied the ef... Read more »
Genome-wide DNA methylation analysis in Graves' disease. Published: January, 2015 Abstract:
As an autoimmune disease, Graves' disease (GD) is associated with many genetic and environmental risk factors. Although the exact mechanism remains unclear, epigenetic determinants, such as DNA methylation, are thought to contribute to the pathoge... Read more »
Ultra-low-input native ChIP-seq for rare cell populations Published: January, 2015 Abstract:
Combined chromatin immunoprecipitation and next-generation sequencing (ChIP-seq) has enabled genome-wide epigenetic profiling of numerous cell lines and tissue types. A major limitation of ChIP-seq, however, is the large number of cells required t... Read more »
Mutated in colorectal cancer (MCC) is a novel oncogene in B lymphocytes. Published: September, 2014 Abstract:
BackgroundIdentification of novel genetic risk factors is imperative for a better understanding of B lymphomagenesis and for the development of novel therapeutic strategies. TRAF3, a critical regulator of B cell survival, was recently recognized a... Read more »
KMTase Set7/9 is a critical regulator of E2F1 activity upon genotoxic stress. Published: August, 2014 Abstract:
During the recent years lysine methyltransferase Set7/9 ((Su(var)-3-9, Enhancer-of-Zeste, Trithorax) domain containing protein 7/9) has emerged as an important regulator of different transcription factors. In this study, we report a novel function... Read more »
Epigenetics and the Evolution of Darwin's Finches. Published: July, 2014 Abstract:
The prevailing theory for the molecular basis of evolution involves genetic mutations that ultimately generate the heritable phenotypic variation on which natural selection acts. However, epigenetic transgenerational inheritance of phenotypic vari... Read more »
RNAi-Mediated Gene silencing in Zebrafish Triggered by Convergent Transcription. Published: June, 2014 Abstract:
RNAi based strategies to induce gene silencing are commonly employed in numerous model organisms but have not been extensively used in zebrafish. We found that introduction of transgenes containing convergent transcription units in zebrafish embry... Read more »
DNMT3L promotes quiescence in postnatal spermatogonial progenitor cells. Published: June, 2014 Abstract:
The ability of adult stem cells to reside in a quiescent state is crucial for preventing premature exhaustion of the stem cell pool. However, the intrinsic epigenetic factors that regulate spermatogonial stem cell quiescence are largely unknown. H... Read more »
Dendritic cell development requires histone deacetylase activity. Published: May, 2014 Abstract:
DCs develop from multipotent progenitors (MPPs), which commit into DC-restricted common dendritic cell progenitors (CDPs). CDPs further differentiate into classical DCs (cDCs) and plasmacytoid DCs (pDCs). Here, we studied the impact of histone ace... Read more »
Myostatin Regulates Energy Homeostasis in the Heart and Prevents Heart Failure. Published: May, 2014 Abstract:
RATIONALE: Myostatin is a major negative regulator of skeletal muscle mass and initiates multiple metabolic changes including enhanced insulin sensitivity. However, the function of Myostatin in the heart is barely understood although it is upregul... Read more »
TAL effector-mediated genome visualization (TGV). Published: April, 2014 Abstract:
The three-dimensional remodeling of chromatin within nucleus is being recognized as determinant for genome regulation. Recent technological advances in live imaging of chromosome loci begun to explore the biological roles of the movement of the ch... Read more »
Persistent STAT5 activation in myeloid neoplasms recruits p53 into gene regulation. Published: March, 2014 Abstract:
STAT (Signal Transducer and Activator of Transcription) transcription factors are constitutively activated in most hematopoietic cancers. We previously identified a target gene, LPP/miR-28 (LIM domain containing preferred translocation partner in ... Read more »
An increase in MECP2 dosage impairs neural tube formation. Published: March, 2014 Abstract:
Epigenetic mechanisms are fundamental for shaping the activity of the central nervous system (CNS). Methyl-CpG binding protein 2 (MECP2) acts as a bridge between methylated DNA and transcriptional effectors responsible for differentiation programs... Read more »
Immune evasion by oncogenic proteins of acute myeloid leukemia. Published: March, 2014 Abstract:
PML-RARA and AML1-ETO are important oncogenic fusion proteins that play a central role in transformation to acute myeloid leukemia (AML). Whether these fusion proteins render the tumor cells with immune evasion properties is unknown. Here we show ... Read more »
Principles of nucleation of H3K27 methylation during embryonic development. Published: March, 2014 Abstract:
During embryonic development, maintenance of cell identity and lineage commitment requires the Polycomb-group PRC2 complex, which catalyzes histone H3 lysine 27 trimethylation (H3K27me3). However, the developmental origins of this regulation are u... Read more »
Epigenomic alterations define lethal CIMP-positive ependymomas of infancy. Published: February, 2014 Abstract:
Ependymomas are common childhood brain tumours that occur throughout the nervous system, but are most common in the paediatric hindbrain. Current standard therapy comprises surgery and radiation, but not cytotoxic chemotherapy as it does not furth... Read more »
Epigenetic upregulation of endogenous VEGF-A reduces myocardial infarct size in mice. Published: February, 2014 Abstract:
"Epigenetherapy" alters epigenetic status of the targeted chromatin and modifies expression of the endogenous therapeutic gene. In this study we used lentiviral in vivo delivery of small hairpin RNA (shRNA) into hearts in a murine infarction model... Read more »
H19 lncRNA controls gene expression of the Imprinted Gene Network by recruiting MBD1. Published: December, 2013 Abstract:
The H19 gene controls the expression of several genes within the Imprinted Gene Network (IGN), involved in growth control of the embryo. However, the underlying mechanisms of this control remain elusive. Here, we identified the methyl-CpG-binding ... Read more »
HDAC inhibitor confers radiosensitivity to prostate stem-like cells. Published: December, 2013 Abstract:
Background:Radiotherapy can be an effective treatment for prostate cancer, but radiorecurrent tumours do develop. Considering prostate cancer heterogeneity, we hypothesised that primitive stem-like cells may constitute the radiation-resistant frac... Read more »
A key role for EZH2 in epigenetic silencing of HOX genes in mantle cell lymphoma. Published: December, 2013 Abstract:
The chromatin modifier EZH2 is overexpressed and associated with inferior outcome in mantle cell lymphoma (MCL). Recently, we demonstrated preferential DNA methylation of HOX genes in MCL compared with chronic lymphocytic leukemia (CLL), despite t... Read more »
Dynamic reprogramming of 5-hydroxymethylcytosine during early porcine embryogenesis. Published: November, 2013 Abstract:
DNA active demethylation is an important epigenetic phenomenon observed in porcine zygotes, yet its molecular origins are unknown. Our results show that 5-methylcytosine (5mC) converts into 5-hydroxymethylcytosine (5hmC) during the first cell cycl... Read more »
Live visualization of chromatin dynamics with fluorescent TALEs. Published: November, 2013 Abstract:
The spatiotemporal organization of genomes in the nucleus is an emerging key player to regulate genome function. Live imaging of nuclear organization dynamics would be a breakthrough toward uncovering the functional relevance and mechanisms regula... Read more »
Dimethyl fumarate regulates histone deacetylase expression in astrocytes. Published: October, 2013 Abstract:
We previously showed that dimethyl fumarate (DMF) reduces inflammatory activation in astrocytes, involving activation of transcription factor Nrf2. However, the pathways causing Nrf2 activation were not examined. We now show that DMF modifies expr... Read more »
Combined modulation of polycomb and trithorax genes rejuvenates β cell replication. Published: October, 2013 Abstract:
Inadequate functional β cell mass underlies both type 1 and type 2 diabetes. β Cell growth and regeneration also decrease with age through mechanisms that are not fully understood. Age-dependent loss of enhancer of zeste homolog 2 (EZH2) prevents ... Read more »
A Kinase-Independent Function of CDK6 Links the Cell Cycle to Tumor Angiogenesis. Published: August, 2013 Abstract:
In contrast to its close homolog CDK4, the cell cycle kinase CDK6 is expressed at high levels in lymphoid malignancies. In a model for p185(BCR-ABL+) B-acute lymphoid leukemia, we show that CDK6 is part of a transcription complex that induces the ... Read more »
Thalamic control of neocortical area formation in mice. Published: May, 2013 Abstract:
The mammalian neocortex undergoes dramatic transformation during development, from a seemingly homogenous sheet of neuroepithelial cells into a complex structure that is tangentially divided into discrete areas. This process is thought to be contr... Read more »
Naive pluripotency is associated with global DNA hypomethylation. Published: March, 2013 Abstract:
Naive pluripotent embryonic stem cells (ESCs) and embryonic germ cells (EGCs) are derived from the preimplantation epiblast and primordial germ cells (PGCs), respectively. We investigated whether differences exist between ESCs and EGCs, in view of... Read more »
Dynamics of 5-hydroxymethylcytosine and chromatin marks in Mammalian neurogenesis. Published: February, 2013 Abstract:
DNA methylation in mammals is highly dynamic during germ cell and preimplantation development but is relatively static during the development of somatic tissues. 5-hydroxymethylcytosine (5hmC), created by oxidation of 5-methylcytosine (5mC) by Tet... Read more »
Interplay between KLF4 and ZEB2/SIP1 in the regulation of E-cadherin expression Published: January, 2013 Abstract:
E-cadherin expression is repressed by ZEB2/SIP1 while it is induced by KLF4. Independent data from the literature indicate that these two transcription factors could bind close to each other in the proximal region of the E-cadherin gene promoter. ... Read more »
Limitations and possibilities of low cell number ChIP-seq. Published: November, 2012 Abstract:
ABSTRACT: BACKGROUND: Chromatin immunoprecipitation coupled with high-throughput DNA sequencing (ChIP-seq) offers high resolution, genome-wide analysis of DNA-protein interactions. However, current standard methods require abundant starting materi... Read more »
Inhibition of Tumor Promotion by Parthenolide: Epigenetic Modulation of p21. Published: November, 2012 Abstract:
The promotion stage in the multistep process of epidermal tumorigenesis is NF-кB-dependent, epigenetically regulated, and reversible, thus, a suitable target for chemoprevention. We investigated whether the NF-кB inhibitor, parthenolide, currently... Read more »
Non-genotoxic carcinogen exposure induces defined changes in the 5-hydroxymethylome. Published: October, 2012 Abstract:
ABSTRACT: BACKGROUND: Induction and promotion of liver cancer by exposure to non-genotoxic carcinogens coincides with epigenetic perturbations, including specific changes in DNA methylation. Here we investigate the genome-wide dynamics of 5-hydro... Read more »
Association of UHRF1 with methylated H3K9 directs the maintenance of DNA methylation. Published: September, 2012 Abstract:
A fundamental challenge in mammalian biology has been the elucidation of mechanisms linking DNA methylation and histone post-translational modifications. Human UHRF1 (ubiquitin-like PHD and RING finger domain-containing 1) has multiple domains tha... Read more »
p53-Independent regulation of p21Waf1/Cip1 expression and senescence by PRMT6. Published: September, 2012 Abstract:
p21 is a potent cyclin-dependent kinase inhibitor that plays a role in promoting G1 cell cycle arrest and cellular senescence. Consistent with this role, p21 is a downstream target of several tumour suppressors and oncogenes, and it is downregulat... Read more »
Multigenerational epigenetic adaptation of the hepatic wound-healing response. Published: September, 2012 Abstract:
We investigated whether ancestral liver damage leads to heritable reprogramming of hepatic wound healing in male rats. We found that a history of liver damage corresponds with transmission of an epigenetic suppressive adaptation of the fibrogenic ... Read more »
Chromatin Immunoprecipitation Analysis of Xenopus Embryos Published: August, 2012 Abstract:
Chromatin immunoprecipitation (ChIP) is a powerful technique to study epigenetic regulation and transcription factor binding events in the nucleus. It is based on immune-affinity capture of epitopes that have been cross-linked to genomic DNA in vi... Read more »
Intronic RNAs mediate EZH2 regulation of epigenetic targets. Published: June, 2012 Abstract:
Epigenetic deregulation at a number of genomic loci is one of the hallmarks of cancer. A role for some RNA molecules in guiding repressive polycomb complex PRC2 to specific chromatin regions has been proposed. Here we use an in vivo cross-linking ... Read more »
Functional Genomic Methods to Study Estrogen Receptor Activity. Published: May, 2012 Abstract:
Estrogen Receptor (ER) is a nuclear receptor that mediates the actions of estrogen and tamoxifen. ER is expressed in a major fraction of human breast cancers. Recently, genomic maps for estrogen- and tamoxifen-ER have been published. Interestingly... Read more »
The histone demethylase Kdm3a is essential to progression through differentiation. Published: May, 2012 Abstract:
Histone demethylation has important roles in regulating gene expression and forms part of the epigenetic memory system that regulates cell fate and identity by still poorly understood mechanisms. Here, we examined the role of histone demethylase K... Read more »
Lxrα Regulates the Androgen Response in Prostate Epithelium. Published: April, 2012 Abstract:
Benign prostatic hyperplasia is a nonmalignant enlargement of the prostate that commonly occurs in older men. We show that liver X receptor (Lxr)-α knockout mice (lxrα(-/-)) develop ventral prostate hypertrophy, correlating with an overaccumulatio... Read more »
The transcriptional and epigenomic foundations of ground state pluripotency. Published: April, 2012 Abstract:
Mouse embryonic stem (ES) cells grown in serum exhibit greater heterogeneity in morphology and expression of pluripotency factors than ES cells cultured in defined medium with inhibitors of two kinases (Mek and GSK3), a condition known as "2i" pos... Read more »
HDAC1 Regulates Fear Extinction in Mice. Published: April, 2012 Abstract:
Histone acetylation has been implicated with the pathogenesis of neuropsychiatric disorders and targeting histone deacetylases (HDACs) using HDAC inhibitors was shown to be neuroprotective and to initiate neuroregenerative processes. However, litt... Read more »
Anticheckpoint pathways at telomeres in yeast Published: February, 2012 Abstract:
Telomeres hide (or ‘cap’) chromosome ends from DNA-damage surveillance mechanisms that arrest the cell cycle and promote repair, but the checkpoint status of telomeres is not well understood. Here we characterize the response in Saccharomyces cere... Read more »
Control of ground-state pluripotency by allelic regulation of Nanog. Published: February, 2012 Abstract:
Pluripotency is established through genome-wide reprogramming during mammalian pre-implantation development, resulting in the formation of the naive epiblast. Reprogramming involves both the resetting of epigenetic marks and the activation of plur... Read more »
Mechanisms and functions of Tet protein-mediated 5-methylcytosine oxidation. Published: December, 2011 Abstract:
Ten-eleven translocation 1-3 (Tet1-3) proteins have recently been discovered in mammalian cells to be members of a family of DNA hydroxylases that possess enzymatic activity toward the methyl mark on the 5-position of cytosine (5-methylcytosine [5... Read more »
Distinct Epigenomic Features in End-Stage Failing Human Hearts Published: November, 2011 Abstract:
Background—The epigenome refers to marks on the genome, including DNA methylation and histone modifications, that regulate the expression of underlying genes. A consistent profile of gene expression changes in end-stage cardiomyopathy led us to hy... Read more »
CTCF-promoted RNA polymerase II pausing links DNA methylation to splicing. Published: October, 2011 Abstract:
Alternative splicing of pre-messenger RNA is a key feature of transcriptome expansion in eukaryotic cells, yet its regulation is poorly understood. Spliceosome assembly occurs co-transcriptionally, raising the possibility that DNA structure may di... Read more »
The human histone H3 complement anno 2011. Published: October, 2011 Abstract:
Histones are highly basic, relatively small proteins that complex with DNA to form higher order structures that underlie chromosome topology. Of the four core histones H2A, H2B, H3 and H4, it is H3 that is most heavily modified at the post-transla... Read more »
DNA methylation profiles of human active and inactive X chromosomes. Published: October, 2011 Abstract:
X-chromosome inactivation (XCI) is a dosage compensation mechanism that silences the majority of genes on one X chromosome in each female cell. To characterize epigenetic changes that accompany this process, we measured DNA methylation levels in 4... Read more »
Histone tail acetylation in brain occurs in an unpredictable fashion after death. Published: September, 2011 Abstract:
Histone acetylation plays a role in the regulation of gene transcription. Yet it is not known whether post-mortem brain tissue is suitable for the analysis of histone acetylation. To examine this question, nucleosomes were isolated from frontal co... Read more »
