Dual roles of histone H3 lysine-4 in antagonizing Polycomb group function and promoting target gene expression
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PROVIDER: PRJNA1143547 | ENA |
REPOSITORIES: ENA
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Project description:Tight control over cell identity gene expression is necessary for proper adult form and function. The opposing activities of Polycomb and trithorax complexes determine the ON/OFF state of targets like the Hox genes. Trithorax encodes a methyltransferase specific to histone H3 lysine-4 (H3K4). However, there is no direct evidence that H3K4 regulates Polycomb group target genes in vivo. Here, we demonstrate two key roles for replication-dependent histone H3.2K4 in target control. We find that H3.2K4 antagonizes Polycomb group catalytic activity and that it is required for proper target gene activation. We conclude that H3.2K4 directly regulates expression of Polycomb targets.
2024-12-18 | GSE273885 | GEO
Project description:Polycomb complexes regulate cell-type specific gene expression programs through heritable silencing of target genes. Trimethylation of histone H3 lysine 27 (H3K27me3) is essential for this process. Perturbation of H3K36 is thought to interfere with H3K27me3. We show that mutants of Drosophila replication-dependent (H3.2K36R) or -independent (H3.3K36R) histone H3 genes generally maintain Polycomb silencing and reach later stages of development. In contrast, combined (H3.3K36RH3.2K36R) mutants display widespread Hox gene misexpression and fail to develop past the first larval instar. Chromatin profiling showed that the H3.2K36R mutation disrupts H3K27me3 levels broadly and significantly throughout silenced domains, whereas these regions are mostly unaffected in H3.3K36R animals. Analysis of H3.3 distributions showed that this histone is enriched at presumptive PREs (Polycomb Response Elements) located outside of silenced domains but relatively depleted from those inside. We conclude that H3.2 and H3.3 K36 residues collaborate to repress Hox genes via distinct genomic subcompartments and mechanisms.
2023-02-06 | GSE215017 | GEO
Project description:Distinct roles for canonical and variant histone H3 lysine 36 in polycomb silencing
| PRJNA888082 | ENA
Project description:Polycomb group proteins are transcriptional repressors that play essential roles in regulating genes required for differentiation and embryonic development. The Polycomb repressive complex 2 (PRC2) contains the methyltransferase activity for lysine 27 on histone 3 (H3K27me3), which is a docking site for the PRC1 complex and leads to gene repression. However, the role of other histone modifications in regulating PRC2 activity is just beginning to be understood. Here we show that direct recognition of histone H3 methylated at lysine 36 (H3K36me), an mark associated with activation, by the PRC2 subunit Phf19 is required for the full enzymatic activity of the PRC2 complex. We provide structural evidence for this interaction by nuclear magnetic resonance spectroscopy (NMR). Using genome-wide chromatin binding analyses and expression analyses, we show that Phf19 binds to a subset of PRC2 targets in embryonic stem (ES) cells, and that this is required for their repression and for H3K27me3 deposition. These findings reveal that the H3K36me2/3-Phf19 interaction is essential for PRC2 complex activity and for proper regulation of gene repression in ES cells. We determined the genome binding/occupancy profile of Phf19, H3K36me3, H3K36me2, H3K27me3 and Suz12 by high throughput sequencing in mouse embryonic stem cells. For Phf19 two independent biological replicas were performed and Phf19 binding sites were defined as those sites (ChIP-seq peaks) present in both replicas. H3K27me3 was evaluated in control ES cells and cells depleted of Phf19 (shRd and shPhf19 respectively).
2012-10-16 | E-GEOD-41589 | biostudies-arrayexpress
Project description:Polycomb group proteins are transcriptional repressors that play essential roles in regulating genes required for differentiation and embryonic development. The Polycomb repressive complex 2 (PRC2) contains the methyltransferase activity for lysine 27 on histone 3 (H3K27me3), which is a docking site for the PRC1 complex and leads to gene repression. However, the role of other histone modifications in regulating PRC2 activity is just beginning to be understood. Here we show that direct recognition of histone H3 methylated at lysine 36 (H3K36me), an mark associated with activation, by the PRC2 subunit Phf19 is required for the full enzymatic activity of the PRC2 complex. We provide structural evidence for this interaction by nuclear magnetic resonance spectroscopy (NMR). Using genome-wide chromatin binding analyses and expression analyses, we show that Phf19 binds to a subset of PRC2 targets in embryonic stem (ES) cells, and that this is required for their repression and for H3K27me3 deposition. These findings reveal that the H3K36me2/3-Phf19 interaction is essential for PRC2 complex activity and for proper regulation of gene repression in ES cells.
2012-10-16 | GSE41589 | GEO
Project description:Polycomb Repressor Complex 2 (PRC2) is a multi-protein epigenetic regulator complex that plays critical roles in early development and tissue differentiation. The complex catalyzes the methylation of histone H3 lysine 27 (H3K27). The tri-methyl state (H3K27me3) is well studied as an agent of gene repression, but more recently distinct roles for the mono- and di-methyl states have been discovered. In order to more fully understand how PRC2-associated factors might influence H3K27 status, we screened for physical associations of PRC2 subunits. Knockdown of these factors was used to produce functional interaction maps focused on H3K27 methylation, including proteins that have positive and negative effects on the levels each histone mark.
2018-04-05 | PXD005381 | Pride
Project description:This SuperSeries is composed of the following subset Series: GSE18588: CpG islands recruit a histone H3 lysine 36 demethylase [Illumina sequencing data] GSE21201: CpG islands recruit a histone H3 lysine 36 demethylase [Agilent data] Refer to individual Series
2010-04-26 | E-GEOD-21202 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE29146: NSD2 links dimethylation of histone H3 at lysine 36 to oncogenic programming [ChIP] GSE29147: NSD2 links dimethylation of histone H3 at lysine 36 to oncogenic programming [RNAi] GSE29148: NSD2 links dimethylation of histone H3 at lysine 36 to oncogenic programming [TKO] GSE29150: NSD2 links dimethylation of histone H3 at lysine 36 to oncogenic programming [Transduction] Refer to individual Series
2011-11-29 | E-GEOD-29305 | biostudies-arrayexpress
Project description:G9a/GLP and Polycomb Repressive Complex 2 (PRC2) are two major epigenetic silencing machineries, which in particular methylate histone H3 on lysines 9 and 27 (H3K9 and H3K27), respectively. Although evidence of a crosstalk between H3K9 and H3K27 methylations has started to emerge, their actual interplay remains elusive. Here, we show that PRC2 and G9a/GLP interact physically and functionally. Moreover, combining different genome-wide approaches, we demonstrate that Ezh2 and G9a/GLP share an important number of common genomic targets, encoding developmental and neuronal regulators. Furthermore, we show that G9a enzymatic activity modulates PRC2 genomic recruitment to a subset of its target genes. Taken together, our findings demonstrate an unanticipated interplay between two main histone lysine methylation mechanisms, which cooperate to maintain silencing of a subset of developmental genes. Microarray has been perform in triplicate on total extract RNA from mES cell (TT2 : Wildtype and KOs G9a-/-, GLP-/-, G9a-/- and GLP-/-)
2014-01-03 | E-GEOD-46544 | biostudies-arrayexpress
Project description:G9a/GLP and Polycomb Repressive Complex 2 (PRC2) are two major epigenetic silencing machineries, which in particular methylate histone H3 on lysines 9 and 27 (H3K9 and H3K27), respectively. Although evidence of a crosstalk between H3K9 and H3K27 methylations has started to emerge, their actual interplay remains elusive. Here, we show that PRC2 and G9a/GLP interact physically and functionally. Moreover, combining different genome-wide approaches, we demonstrate that Ezh2 and G9a/GLP share an important number of common genomic targets, encoding developmental and neuronal regulators. Furthermore, we show that G9a enzymatic activity modulates PRC2 genomic recruitment to a subset of its target genes. Taken together, our findings demonstrate an unanticipated interplay between two main histone lysine methylation mechanisms, which cooperate to maintain silencing of a subset of developmental genes. RNA-seq has been perform in triplicate on mES cell (TT2 : Wildtype, and KO G9a-/-)
2014-01-03 | E-GEOD-49669 | biostudies-arrayexpress