Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

H3K64me3 and H3K9me3 profiling at promoters in mouse embryonic stem cells

ABSTRACT: Histone modifications are central to the regulation of all DNA-dependent processes but the repertoire of known modifications is far from complete. Lysine 64 of Histone H3 (H3K64) lies within the globular domain of H3 at a structurally important position within the nucleosome. We identify tri-methylation of H3K64 (H3K64me3) as a modification enriched in pericentric heterochromatin and associated with repeated sequences and transcriptionally inactive genomic regions. Interestingly, the pericentric enrichment of H3K64me3 depends on the Suv39h methyltransferases. Further, we show that this newly identified mark is dynamically regulated during the two major epigenetic reprogramming events in mammals. In primordial germ cells (PGCs) H3K64me3 is present at the time of specification, but disappears transiently during germline reprogramming. In the early mouse embryo it is inherited exclusively through the maternal germline and specifically enriched in heterochromatic regions of the maternal pronucleus. Subsequently the modification is rapidly removed from the maternal chromatin suggesting an important role for H3K64me3 turnover in development. Taken together, our findings firmly establish H3K64me3 as a novel histone modification mark of repressive chromatin, which displays crosstalk to the Suv39 pathway and is dynamically reprogrammed during development. We hypothesize that methylation of this lysine helps to 'secure' the nucleosome and perhaps the surrounding heterochromatin, in an appropriately repressed state during development. Keywords: ChIP-chip, embryonic stem cells, H3K64me3, H3K9me3, heterochromatin

ORGANISM(S): Mus musculus

PROVIDER: GSE16185 | GEO | 2009/06/28

SECONDARY ACCESSION(S): PRJNA115075

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

H3K64me3 and H3K9me3 profiling at promoters in mouse embryonic stem cells

Project description:Histone modifications are central to the regulation of all DNA-dependent processes but the repertoire of known modifications is far from complete. Lysine 64 of Histone H3 (H3K64) lies within the globular domain of H3 at a structurally important position within the nucleosome. We identify tri-methylation of H3K64 (H3K64me3) as a modification enriched in pericentric heterochromatin and associated with repeated sequences and transcriptionally inactive genomic regions. Interestingly, the pericentric enrichment of H3K64me3 depends on the Suv39h methyltransferases. Further, we show that this newly identified mark is dynamically regulated during the two major epigenetic reprogramming events in mammals. In primordial germ cells (PGCs) H3K64me3 is present at the time of specification, but disappears transiently during germline reprogramming. In the early mouse embryo it is inherited exclusively through the maternal germline and specifically enriched in heterochromatic regions of the maternal pronucleus. Subsequently the modification is rapidly removed from the maternal chromatin suggesting an important role for H3K64me3 turnover in development. Taken together, our findings firmly establish H3K64me3 as a novel histone modification mark of repressive chromatin, which displays crosstalk to the Suv39 pathway and is dynamically reprogrammed during development. We hypothesize that methylation of this lysine helps to 'secure' the nucleosome and perhaps the surrounding heterochromatin, in an appropriately repressed state during development. Keywords: ChIP-chip, embryonic stem cells, H3K64me3, H3K9me3, heterochromatin ChIP-chip experiments were performed with four independent biological replicates for H3K64me3 and two independent replicates for H3K9me3. For each condition hybridizations include a dye-swap experiment.

2010-05-16 | E-GEOD-16185 | biostudies-arrayexpress

The INO80 complex regulates epigenetic inheritance of heterochromatin (ChIP-seq, Mnase-seq)

Project description:One key aspect of epigenetic inheritance is that chromatin structure can be stably inherited through generations even after removal of the signal that establishes such structure. In fission yeast, the RNA interference (RNAi) machinery is critical for initial targeting of histone methyltransferase Clr4 to pericentric repeats to establish heterochromatin. However, pericentric heterochromatin cannot be properly inherited in the absence of RNAi, suggesting the existence of mechanisms that counteract chromatin structure inheritance. Here we show that in the absence of certain components of the INO80 chromatin-remodeling complex, pericentric heterochromatin can be properly inherited in RNAi mutants. The ability of INO80 to counter heterochromatin inheritance is attributed to one accessory subunit Iec5, which promotes histone turnover at heterochromatin regions, but has little effects on nucleosome positioning at heterochromatin, gene expression, or the DNA damage response. Slow histone turnover preserves parental histones at repeat regions to enhance epigenetic inheritance of heterochromatin not only in RNAi mutants but also in wild type cells. Our analyses demonstrate the importance of INO80 in controlling heterochromatin inheritance and maintaining the proper heterochromatin landscape of the genome.

2020-11-18 | GSE150542 | GEO

Dynamically reorganized chromatin is the key for the reprogramming of somatic cells to pluripotent cells

Project description:We investigated genome-wide nucleosome coverage and histone methylation occupancies in somatic MEFs, intermediate pre-iPSCs and fully reprogrammed iPSCs. We found that nucleosome occupancies increased in promoter regions and decreased in intergenic regions in pre-iPSCs and then recover to an intermediate level in iPSCs. Nucleosomes in pre-iPSCs are much more phased than those in MEFs and iPSCs. Bivalent, active, repressive domains are cell type-specific and change dynamically during reprogramming. HCG and LCG promoters exhibit distinct nucleosome occupancy patterns and are dynamically marked by H3K4me3/H3K27me3 during reprogramming, correspondingly showing different gene activities. Surprisingly, Vitamin C promotes nucleosome reorganization from pre-iPSCs to iPSCs. CTCF binding sites change dynamically during reprogramming, though they share a conserved binding motif. Nucleosome occupies CTCF sites to a higher extent in pre-iPSCs than those in MEFs and iPSCs. Taken together, our study reveals that dynamic changes of nucleosome positioning and chromatin organization associated gene regulation during reprogramming. Examine dynamics of nucleosome positioning and histone modification profiles as well as gene expression regulation during somatic cell reprogramming

2015-12-13 | E-GEOD-60627 | biostudies-arrayexpress

MCAF2/ATF7IP2 directs meiosis-specific H3K9 methylation

Project description:H3K9 tri-methylation (H3K9me3) has emerging functions in gene regulation in addition to its accumulation on constitutive heterochromatin at pericentromeres. It remains a mystery why and how H3K9me3 is dynamically regulated in male meiosis. Here, we identify a novel and critical regulator of H3K9 methylation and spermatogenic heterochromatin organization: the germline-specific protein MCAF2 (ATF7IP2). We show that MCAF2 amasses on autosomal and X pericentric heterochromatin in male germ cells. On the sex chromosomes, which undergo meiotic sex chromosome inactivation (MSCI), the DNA damage response pathway recruits MCAF2 to X pericentric heterochromatin, where it facilitates the recruitment of SETDB1, a histone methyltransferase that catalyzes H3K9me3. In the absence of MCAF2, germ cells are arrested in meiotic prophase, and the mutant analyses revealed that MCAF2 is required for the maintenance of MSCI, and for global activation of autosomal genes and retrotransposon-derived loci in meiosis; this reveals a regulatory function for MCAF2 that is counterintuitive to its association with repressive H3K9me3. Taken together, we propose that MCAF2 is a downstream effector of the DDR pathway in meiosis that coordinates the organization of heterochromatin and gene regulation through the spatial regulation of SETDB1-mediated H3K9me3 deposition.

2024-02-22 | GSE223742 | GEO

High Resolution Mapping of H1 Linker Histone Variants in Embryonic Stem Cells

Project description:H1 linker histones facilitate higher order chromatin folding and are essential for mammalian development. To achieve high resolution mapping of H1 variants H1d and H1c in embryonic stem cells (ESCs), we have established a knock-in system and shown that the N-terminally tagged H1 proteins are functionally interchangeable to their endogenous counterparts in vivo. H1d and H1c are depleted from GC- and gene-rich regions and active promoters, inversely correlated with H3K4me3, but positively correlated with H3K9me3 and associated with characteristic sequence features. Surprisingly, both H1d and H1c are significantly enriched at major satellites, which display increased nucleosome spacing compared with bulk chromatin. While also depleted at active promoters and enriched at major satellites, overexpressed H10 displays differential binding patterns in specific repetitive sequences compared with H1d and H1c. Depletion of H1c, H1d and H1e causes pericentric chromocenter clustering and de-repression of major satellites. These results integrate the localization of an understudied type of chromatin proteins, namely the H1 variants, into the epigenome map of mouse ESCs, and we identify significant changes at pericentric heterochromatin upon depletion of this epigenetic mark. Mapping linker histone H1 variants H1d, H1c and H10 as well as 3 core histone modifications in mouse ESC genome.

2013-04-29 | E-GEOD-46134 | biostudies-arrayexpress

Silencing of pericentric heterochromatin associated with SIRT6-dependent H3K18 deacetylation protects against mitotic errors and cellular senescence

Project description:Pericentric heterochromatin silencing at mammalian centromeres is essential for mitotic fidelity and genomic stability. Defective pericentric silencing is observed in senescent cells, aging tissues, and mammalian tumors, but the underlying mechanisms and functional consequences of these defects are unclear. Here, we uncover a pivotal role of the human SIRT6 enzyme in pericentric transcriptional silencing, and this function protects against mitotic defects, genomic instability, and cellular senescence. At pericentric heterochromatin, SIRT6 promotes deacetylation of a new substrate, histone H3 lysine K18 (H3K18), and inactivation of SIRT6 in cells leads to H3K18 hyperacetylation and aberrant accumulation of pericentric transcripts. Strikingly, RNAi-depletion of these transcripts rescues the mitotic and senescence phenotypes of SIRT6-deficient cells. Together, our findings reveal a new function for SIRT6 and H3K18Ac regulation at heterochromatin, and demonstrate the pathogenic role of de-regulated pericentric transcription in aging- and cancer- related cellular dysfunction. H3K18ac, H3K9ac, H3K9me3, H3K56ac and Input ChIP-seq for U2OS cell

2016-04-04 | E-GEOD-69809 | biostudies-arrayexpress

ChIP-Seq of fly Schneider S2 cells to investigate CID islands

Project description:The centromere-specific Histone H3-variant CENH3 (also known as CENP-A) is considered to be an epigenetic mark for establishment and propagation of centromere identity. Pulse-induction of CENH3 (Drosophila CID) in Schneider S2 cells incorporates into noncentromeric regions and generates CID islands that resist clearing from chromosome arms for multiple cell generations. We demonstrate that CID islands represent functional ectopic kinetochores, which are non-randomly distributed on the chromosome and display a preferential localization near telomeres and pericentric heterochromatin in transcriptionally silent, intergenic chromatin domains. Although overexpression of heterochromatin protein 1 (HP1) or increasing Histone acetylation interferes with CID islands formation on a global scale, induction of a locally defined region of synthetic heterochromatin by targeting HP1-LacI fusions to stably integrated Lac Operator arrays produces a proximal hotspot for CID islands formation. These data suggest that the characteristics of regions bordering heterochromatin promote de novo kinetochore assembly and thereby contribute to centromere identity.

2011-07-15 | E-MTAB-652 | biostudies-arrayexpress

The INO80 complex regulates epigenetic inheritance of heterochromatin (RNA-seq)

Project description:One key aspect of epigenetic inheritance is that chromatin structure can be stably inherited through generations even after removal of the initial signal that establishes such structure. In fission yeast, the RNA interference (RNAi) machinery is critical for the targeting of histone methyltransferase Clr4 to repetitive DNA elements to establish a large domain of heterochromatin marked with histone H3 lysine 9 methylation (H3K9me). Subsequently during DNA replication, the deposition of parental histones containing H3K9me into daughter DNA strands is expected to recruit Clr4 to modify neighboring new histones, resulting in the inheritance of heterochromatin in both daughter cells. However, pericentric heterochromatin cannot be properly inherited in the absence of RNAi, suggesting the existence of mechanisms that counteract chromatin-based inheritance. Here we show that in the absence of certain components of the INO80 chromatin remodeling complex, pericentric heterochromatin can be properly inherited in RNAi mutants. The ability of INO80 to counter heterochromatin inheritance is attributed to one accessory subunit Iec5, which promotes histone turn over at heterochromatin regions, but has little effects on the ability of INO80 in regulating nucleosome positioning at heterochromatin, gene expression, or the DNA damage response. Slow histone turnover preserves parental histones at repeat regions to enhance epigenetic inheritance of heterochromatin not only in RNAi mutants but also in wild type cells. Our analyses identified a separation-of-function mutation of INO80 in regulating histone turnover at heterochromatin and demonstrate the important role of histone turnover in controlling heterochromatin inheritance and maintaining the proper heterochromatin landscape of the genome.

2020-11-18 | GSE150544 | GEO

Dnmt3l-/+ (maternal methylation-deficient) vs normal 8.5dpc embryos

Project description:During oogenesis, DNA methyltransferase 3-like (Dnmt3l) is required for the establishment of the maternal germline DNA methylation imprints that in the offspring, govern the parent-of-origin-specific expression of most known imprinted genes (Science 2001, 294:2536-9). Dnmt3l-deficient dams were crossed with wildtype sires to obtain Dnmt3l-/+ embryos that lack maternal methylation imprints. Gene expression was measured in Dnmt3l-/+ and wildtype embryos and is expected to differ for imprinted genes that are under the control of a maternal methylation mark. Keywords: genetic modification, DNA methylation

2008-04-14 | GSE8756 | GEO

ATF7IP2/MCAF2 directs H3K9 methylation and meiotic gene regulation in the male germline [RNA-Seq]

Project description:H3K9 tri-methylation (H3K9me3) plays emerging roles in gene regulation, beyond its accumulation on pericentric constitutive heterochromatin. It remains a mystery why and how H3K9me3 undergoes dynamic regulation in male meiosis. Here, we identify a novel, critical regulator of H3K9 methylation and spermatogenic heterochromatin organization: the germline-specific protein ATF7IP2 (MCAF2). We show that, in male meiosis, ATF7IP2 amasses on autosomal and X pericentric heterochromatin, spreads through the entirety of the sex chromosomes, and accumulates on thousands of autosomal promoters and retrotransposon loci. On the sex chromosomes, which undergo meiotic sex chromosome inactivation (MSCI), the DNA damage response pathway recruits ATF7IP2 to X pericentric heterochromatin, where it facilitates the recruitment of SETDB1, a histone methyltransferase that catalyzes H3K9me3. In the absence of ATF7IP2, male germ cells are arrested in meiotic prophase. Analyses of ATF7IP2-deficient meiosis reveal the protein’s essential roles in the maintenance of MSCI, suppression of retrotransposons, and global activation of autosomal genes. We propose that ATF7IP2 is a downstream effector of the DDR pathway in meiosis that coordinates the organization of heterochromatin and gene regulation through the spatial regulation of SETDB1-mediated H3K9me3 deposition. We performed gene expression analysis using data obtained from RNA-seq of Atf7ip2+/+ and Atf7ip2-/- pachytene spermatocytes.

2024-02-14 | GSE244087 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data