Loss of SETD1B results in the redistribution of genomic H3K4me3 in the oocyte [PBAT]
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PROVIDER: PRJNA705713 | ENA |
REPOSITORIES: ENA
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Project description:Histone 3 lysine 4 trimethylation (H3K4me3) is an epigenetic mark found at active gene promoters and CpG islands. H3K4me3 is essential for mammalian development, yet mechanisms underlying its genomic targeting are poorly understood. H3K4me3 methyltransferases SETD1B and MLL2 are essential for oogenesis. We investigated changes in H3K4me3 in Setd1b conditional knockout (cKO) GV oocytes using ultra-low input ChIP-seq, in complement to DNA methylation and gene expression analysis. Setd1b cKO oocytes showed a redistribution of H3K4me3, with a marked loss at active gene promoters associated with downregulated gene expression. Remarkably, many regions gained H3K4me3 in Setd1b cKOs, in particular those that were DNA hypomethylated, transcriptionally inactive and CpG-rich. All of these are hallmarks of MLL2 targets; thus, loss of SETD1B appears to enable enhanced MLL2 activity. Our work reveals two distinct, complementary mechanisms of genomic targeting of H3K4me3 in oogenesis, with SETD1B linked to transcriptional activity and MLL2 to CpG content.
2022-01-17 | GSE167986 | GEO
Project description:Histone 3 lysine 4 trimethylation (H3K4me3) is an epigenetic mark found at active gene promoters and CpG islands. H3K4me3 is essential for mammalian development, yet mechanisms underlying its genomic targeting are poorly understood. H3K4me3 methyltransferases SETD1B and MLL2 are essential for oogenesis. We investigated changes in H3K4me3 in Setd1b conditional knockout (cKO) GV oocytes using ultra-low input ChIP-seq, in complement to DNA methylation and gene expression analysis. Setd1b cKO oocytes showed a redistribution of H3K4me3, with a marked loss at active gene promoters associated with downregulated gene expression. Remarkably, many regions gained H3K4me3 in Setd1b cKOs, in particular those that were DNA hypomethylated, transcriptionally inactive and CpG-rich. All of these are hallmarks of MLL2 targets; thus, loss of SETD1B appears to enable enhanced MLL2 activity. Our work reveals two distinct, complementary mechanisms of genomic targeting of H3K4me3 in oogenesis, with SETD1B linked to transcriptional activity and MLL2 to CpG content.
2022-01-17 | GSE167985 | GEO
Project description:Histone 3 lysine 4 trimethylation (H3K4me3) is an epigenetic mark found at active gene promoters and CpG islands. H3K4me3 is essential for mammalian development, yet mechanisms underlying its genomic targeting are poorly understood. H3K4me3 methyltransferases SETD1B and MLL2 are essential for oogenesis. We investigated changes in H3K4me3 in Setd1b conditional knockout (cKO) GV oocytes using ultra-low input ChIP-seq, in complement to DNA methylation and gene expression analysis. Setd1b cKO oocytes showed a redistribution of H3K4me3, with a marked loss at active gene promoters associated with downregulated gene expression. Remarkably, many regions gained H3K4me3 in Setd1b cKOs, in particular those that were DNA hypomethylated, transcriptionally inactive and CpG-rich. All of these are hallmarks of MLL2 targets; thus, loss of SETD1B appears to enable enhanced MLL2 activity. Our work reveals two distinct, complementary mechanisms of genomic targeting of H3K4me3 in oogenesis, with SETD1B linked to transcriptional activity and MLL2 to CpG content.
2022-01-17 | GSE167984 | GEO
Project description:Loss of SETD1B results in the redistribution of genomic H3K4me3 in the oocyte
| PRJNA705707 | ENA
Project description:Loss of SETD1B results in the redistribution of genomic H3K4me3 in the oocyte [ChIP-seq]
| PRJNA705711 | ENA
Project description:Loss of SETD1B results in the redistribution of genomic H3K4me3 in the oocyte [RNA-seq]
| PRJNA705709 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2022-01-17 | GSE167987 | GEO
Project description:Germ cell development involves major reprogramming of the epigenome to prime the zygote for totipotency. Histone 3 lysine 4 (H3K4) methylations are universal epigenetic marks mediated in mammals by six H3K4 methyltransferases related to fly Trithorax, including two yeast Set1 orthologs: Setd1a and Setd1b. Whereas Setd1a plays no role in oogenesis, we report that Setd1b deficiency causes female sterility. Oocyte specific Gdf9iCre conditional knockout (Setd1bGdf9cKO) ovaries develop through all stages however follicular loss accumulated with age and unfertilized metaphase II (MII) oocytes exhibited irregularities of the zona pellucida and meiotic spindle. Most Setd1bGdf9cKO zygotes remained in the pronuclear stage and displayed polyspermy in the perivitelline space. Expression profiling of Setd1bGdf9cKO MII oocytes revealed (i) that Setd1b promotes the expression of the major oocyte transcription factors including Obox1, 2, 5, 7, Meis2 and Sall4; and (ii) two-times more up- than downregulated mRNAs suggesting that Setd1b also promotes the expression of negative regulators of oocyte development with multiple Zfp-KRAB factors implicated. Together, these findings indicate that Setd1b serves as maternal effect gene through regulation of the oocyte gene expression program.
2017-02-09 | GSE85360 | GEO
Project description:Histone 3 lysine 4 methylation (H3K4me) is mediated by six different lysine methyltransferases. Amongst these enzymes SET domain containing 1b (SETD1B) has been linked to syndromic intellectual disability but its role in the postnatal brain has not been studied yet. Here we employ mice that lack Setd1b from excitatory neurons of the postnatal forebrain and combine neuron-specific ChIP-seq and RNA-seq approaches to elucidate its role in neuronal gene expression. We observe that SETD1B controls the expression of genes with a broad H3K4me3 peak at their promoters that represent neuronal enriched genes linked to learning and memory function. Comparative analysis to corresponding data from conditional Kmt2a and Kmt2b knockout mice suggests that this function is specific to SETD1B. Moreover, postnatal loss of Setd1b leads to severe learning impairment, suggesting that SETD1B-mediated regulation of H3K4me levels in postnatal neurons is critical for cognitive function.
2021-12-17 | GSE185182 | GEO
Project description:Trimethylation of histone 3 lysine 4 (H3K4me3) is classically thought of as a mark of active promoters and yet it occurs at untranscribed domains. Partial redundancy of H3K4 methyltransferases has made it difficult to delineate the mechanisms underlying genomic targeting of H3K4me3. The oocyte provides an attractive system to investigate this, because extensive acquisition of H3K4me3 occurs in a non-dividing cell and ablation of a single H3K4 methyltransferase, Mll2, prevents most H3K4me3. We developed low-input chromatin immunoprecipitation to interrogate promoter associated histone modifications H3K4me3, H3K27ac and H3K27me3 throughout oogenesis. In non-growing oocytes, H3K4me3 was restricted to transcriptionally active promoters, but as oogenesis progresses, H3K4me3 accumulates in a transcription-independent manner: targeted to broad inter-genic regions, putative enhancers, and transcriptionally silent H3K27me3-marked promoters. Consequently, thousands of bivalent domains are established during oogenesis. Ablation of Mll2 resulted in loss of transcription-independent H3K4me3, with limited effects on transcription-coupled H3K4me3 or gene expression. Deletion of Dnmt3a/b showed that DNA methylation protects regions from acquiring H3K4me3. Our findings show that there are two independent mechanisms of targeting H3K4me3 to genomic elements, with MLL2 recruited to unmethylated CpG-rich regions independently of transcription.
2018-01-01 | GSE93941 | GEO