Chromatin interaction profiles at bivalent genes by multiplexed splinkerette 4C sequencing
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE90782 | GEO | 2017/11/04
SECONDARY ACCESSION(S): PRJNA355885
REPOSITORIES: GEO
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Project description:Regulatory decisions in Drosophila require Polycomb group (PcG) proteins to maintain the silent state and Trithorax group (TrxG) proteins to oppose silencing. Since PcG and TrxG are ubiquitous and lack apparent sequence specificity, a long-standing model is that targeting occurs via protein interactions; for instance, between repressors and PcG proteins. Instead, we found that Pc-repressive complex 1 (PRC1) purifies with coactivators Fs(1)h [female sterile (1) homeotic] and Enok/Br140 during embryogenesis. Fs(1)h is a TrxG member and the ortholog of BRD4, a bromodomain protein that binds to acetylated histones and is a key transcriptional coactivator in mammals. Enok and Br140, another bromodomain protein, are orthologous to subunits of a mammalian MOZ/MORF acetyltransferase complex. Here we confirm PRC1-Br140 and PRC1-Fs(1)h interactions and identify their genomic binding sites. PRC1-Br140 bind developmental genes in fly embryos, with analogous co-occupancy of PRC1 and a Br140 ortholog, BRD1, at bivalent loci in human embryonic stem (ES) cells. We propose that identification of PRC1-Br140 "bivalent complexes" in fly embryos supports and extends the bivalency model posited in mammalian cells, in which the coexistence of H3K4me3 and H3K27me3 at developmental promoters represents a poised transcriptional state. We further speculate that local competition between acetylation and deacetylation may play a critical role in the resolution of bivalent protein complexes during development.
2018-02-22 | GSE104059 | GEO
Project description:Polycomb Group (PcG) proteins regulate gene expression through changes to chromatin structure and are essential for development. PcG proteins function together with the Trithorax Group (TrxG) proteins, which affect diverse steps in transcription activation. The PcG and TrxG are genetically and functionally antagonistic, and current understanding suggests a balance of their activities can maintain a wide range of transcription states. PcG and TrxG proteins assemble into a series of complexes. How these complexes work together, how PcG complexes are recruited to target genes, and whether other proteins are involved in their regulation of gene expression remain open questions. We carried out tandem affinity purification followed by mass spectrometry (TAP-MS) on two core components of Drosophila Polycomb Repressive Complex 1 (PRC1). Our data reveal a network of interactions among PcG complexes, and extensive co-purification of TrxG complexes with PRC1. We co-purified >50 transcription factors with PRC1 that were not previously linked to the PcG. Finally, we identify novel co-purifying complexes, including HP1c and PCNA handling complexes. Our resource of candidate PRC1 interacting proteins generate new hypotheses for PRC1 function.
2023-04-20 | MSV000091759 | MassIVE
Project description:The selective expression is pivotal in orchestrating human development, with the Trithorax Group (TrxG) and Polycomb Group (PcG) complexes playing crucial roles in transcriptional activation and repression, respectively. However, mechanism underlying selective regulation of transcription by TrxG and PcG remains poorly understood. In this study, RYBP was observed to interact with TrxG and PcG components. RYBP and TrxG co-localized loci selectively enriches RING1B. STAT3 enriches at RYBP-TrxG co-localized loci devoid of RING1B, while displaying minimal enrichment at RING1B-enrichred loci. Introduction of STAT3 at RYBP loci disrupted RING1B aggregation and chromatin binding. RYBP-deficiency impairs TrxG deposition at DNA repair genes in RYBP-TrxG loci, consequently diminishing their expression and inducing DNA damage. These results facilitate the transition of embryonic stem cells to 2-cell-like cells. Additionally, RYBP-deficiency attenuates PcG deposition at lineage-specific genes within RYBP-TrxG-RING1B loci, thereby promoting ESC differentiation. Collectively, these results provide novel insights into the selective regulation of gene expression.
2024-04-26 | GSE261485 | GEO
Project description:Drosophila Polycomb group (PcG) and Trithorax group (TrxG) proteins are responsible for the maintenance of stable transcription patterns of many developmental regulators, such as the homeotic genes. We have used a ChIP-on- Chip approach to map the distribution of several PcG/TrxG proteins as well as histone modifications across the two homeotic complexes ANT-C and BX-C. Our data indicate the colocalization of the Polycomb repressive complex 1 (PRC1) with Trx and the DNA binding protein Pleiohomeotic (Pho) at discrete sequence elements as well as significant chromatin assembly differences in active and inactive regions. Trx binds to the promoters of active genes and noncoding transcripts. Most strikingly, in the active state Pho covers extended chromatin domains over many kilobases. The histone modifications investigated, seem to be mutually exclusive, with histone H3 trimethylated at lysine 27 covering inactive chromatin domains whereas hyperacetylated histone H4 is present only at active genes. Keywords: ChIP-chip, cell line comparison
2007-09-25 | GSE7031 | GEO
Project description:The EZH2 histone methyltransferase mediates the humoral immune response and drives lymphomagenesis through de novo formation of bivalent chromatin domains at critical germinal center (GC) B cell promoters. Herein we show that the actions EZH2 in driving GC formation and lymphoma precursor lesions are dependent on the presence of the BCL6 transcriptional repressor, both of which are in turn dependent on the presence of non-canonical PRC1-BCOR complex. BCL6-BCOR complexes assemble preferentially at bivalent promoters in an H3K27me3-dependent manner. We observe specific induction of the CBX8 chromodomain protein in GC B cells. CBX8 binds to H3K27me3 at bivalent promoters and is required for stable association of BCOR complex and its histone modifications. CBX8 loss of function in B cells phenocopies loss of EZH2 and H3K27me3. Moreover, oncogenic BCL6 and EZH2 cooperate to accelerate diffuse large B cell lymphoma (DLBCL) development and combinatorial targeting of these repressors results in enhanced anti-lymphoma activity in vitro, in vivo and in primary human DLBCLs. KDM2B ChIP-sequencing of OCI-Ly1 cells
2016-07-20 | E-GEOD-81623 | biostudies-arrayexpress
Project description:EZH2 mediates the humoral immune response and drives lymphomagenesis through de novo formation of bivalent chromatin domains and critical germinal center (GC) B cell promoters. We show that such formation is dependent on the presense of BCL6 and the presence of non-canonical PRC1-BCOR complex. We observe that BCL6 and EZH2 cooperate to accelerate diffuse large B cell lymphoma (DLBCL) development and combinatorial targeting of these repressors results in enhanced anti-lymphoma activity in vitro, in vivo, and in primary human DLBCLs. DLBCL cell lines treated with BCL6 inhibitor 79-6.1085
2016-07-20 | E-GEOD-73109 | biostudies-arrayexpress
Project description:Bivalent domains marked with repressive H3K27me3 and activating H3K4me2/3 are a molecular signature of totipotency in stem cells and development. While bivalent domains are retained throughout the germline to recover totipotency in the next generation, the mechanisms establishing bivalent domains remains unknown. Here we demonstrate that a germline-specific Polycomb protein, SCML2, binds to chromatin containing hypomethylated DNA to induce H3K27me3, thereby initiating the establishment of germline-specific bivalent domains in mice. SCML2 regulates two distinct classes of autosomal bivalent domains, the first are maintained constitutively through spermatogenesis (Class I), and the second are specifically established during meiosis (Class II). In postmeiotic spermatids, the loss of H3K27me3 leads to an increase of H3K4me2/3 on bivalent domains and disorganization of pericentromic heterochromatin. We propose that SCML2 regulates dynamic bivalent domains in the germline as a molecular imprint to recover totipotency after fertilization.
2018-04-12 | GSE89502 | GEO
Project description:Background: Bivalent chromatin refers to overlapping regions containing activating histone H3 Lys4 trimethylation (H3K4me3) and inactivating H3K27me3 marks. Existence of such bivalent marks on the same nucleosome has only recently been suggested. Previous genome-wide efforts to characterize bivalent chromatin have focused primarily on individual marks to define overlapping zones of bivalency rather than mapping positions of truly bivalent mononucleosomes. Results: Here, we developed an efficacious sequential ChIP technique for examining global positioning of individual bivalent nucleosomes. Using next generation sequencing approaches we show that although individual H3K4me3 and H3K27me3 marks overlap in broad zones, bivalent nucleosomes are focally enriched in the vicinity of the transcription start site (TSS). These seem to occupy the H2A.Z nucleosome positions previously described as salt-labile nucleosomes, and are correlated with low gene expression. Although the enrichment profiles of bivalent nucleosomes show a clear dependency on CpG island content, they demonstrate a stark anti-correlation with methylation status. Conclusions: We show that regional overlap of H3K4me3 and H3K27me3 chromatin tend to be upstream to the TSS, while bivalent nucleosomes with both marks are mainly promoter proximal near the TSS of CpG island-containing genes with poised/low expression. We discuss the implications of the focal enrichment of bivalent nucleosomes around the TSS on the poised chromatin state of promoters in stem cells.
2016-09-13 | GSE86838 | GEO
Project description:In embryonic stem (ES) cells, bivalent chromatin domains with overlapping repressive (H3 lysine 27 tri-methylation) and activating (H3 lysine 4 tri-methylation) histone modifications mark the promoters of more than 2000 genes. To gain insight into the structure and function of bivalent domains, we mapped key histone modifications and subunits of Polycomb repressive complexes 1 and 2 (PRC1 and PRC2) genomewide in human and mouse ES cells by chromatin immunoprecipitation followed by ultra high-throughput sequencing. We find that bivalent domains can be segregated into two classes: the first occupied by both PRC2 and PRC1 (PRC1-positive) and the second specifically bound by PRC2 (PRC2-only). PRC1-positive bivalent domains appear functionally distinct as they more efficiently retain lysine 27 tri-methylation upon differentiation, show stringent conservation of chromatin state, and associate with an overwhelming number of developmental regulator gene promoters. We also used computational genomics to search for sequence determinants of Polycomb binding. This analysis revealed that the genomewide locations of PRC2 and PRC1 can be largely predicted from the locations, sizes and underlying motif contents of CpG islands. We propose that large CpG islands depleted of activating motifs confer epigenetic memory by recruiting the full repertoire of Polycomb complexes. Keywords: cell type comparison Suz12, Ezh2, Ring1b ChIP-Seq in singlicate from mouse embryonic stem (mES) cells. H3K4me3, H3K27me3, H3K36me3, Ezh2 and Ring1b ChIP-Seq in singlicate from human embyonic stem cells (hES; H9).
2008-11-01 | E-GEOD-13084 | biostudies-arrayexpress
Project description:The EZH2 histone methyltransferase mediates the humoral immune response and drives lymphomagenesis through de novo formation of bivalent chromatin domains at critical germinal center (GC) B cell promoters. Herein we show that the actions EZH2 in driving GC formation and lymphoma precursor lesions are dependent on the presence of the BCL6 transcriptional repressor, both of which are in turn dependent on the presence of non-canonical PRC1-BCOR complex. BCL6-BCOR complexes assemble preferentially at bivalent promoters in an H3K27me3-dependent manner. We observe specific induction of the CBX8 chromodomain protein in GC B cells. CBX8 binds to H3K27me3 at bivalent promoters and is required for stable association of BCOR complex and its histone modifications. CBX8 loss of function in B cells phenocopies loss of EZH2 and H3K27me3. Moreover, oncogenic BCL6 and EZH2 cooperate to accelerate diffuse large B cell lymphoma (DLBCL) development and combinatorial targeting of these repressors results in enhanced anti-lymphoma activity in vitro, in vivo and in primary human DLBCLs.
2016-07-20 | GSE81623 | GEO