Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA343011 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR4242552.fastq.gz | Fastqsanger.gz | |||
| SRR4242553.fastq.gz | Fastqsanger.gz | |||
| SRR4242554.fastq.gz | Fastqsanger.gz | |||
| SRR4242555.fastq.gz | Fastqsanger.gz | |||
| SRR4242556.fastq.gz | Fastqsanger.gz |
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Project description:The core Polycomb Repressor Complex 2 (PRC2) is composed of Ezh1/2, Suz12, Eed and is responsible for mediating both H3K27me2 and H3K27me3. However, the mechanisms by which PRC2 demarcates these two repressive modifications in the genome are unknown. In a functional screen, we identified the H3K36 dimethyltransferase Nsd1 as a modulator of PRC2-mediated di- and trimethylation of H3K27. ChIP-Seq analysis following the depletion of Nsd1 revealed a global reduction in H3K36me2 and an increase in H3K27me3 at sites previously marked by H3K27me2. We show that the H3K36me2 at H3K27me2 marks co-occupy regions and provide evidence that the presence of H3K36me2 functions to restrict the spatial distribution of Polycomb mediated H3K27me3 domains.
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Project description:The Polycomb Repressive Complex 2 (PRC2) induces methylation of lysine 27 of histone H3 (H3K27) through its catalytic subunit Ezh2. PRC2-mediated di- and tri-methylation (H3K27me2/me3) have been interchangeably associated with gene repression. However, it remains unclear whether these two degrees of H3K27 methylation have indeed different functions. In this study, we have generated isogenic mouse embryonic stem cells (ESC) with a modified H3K27me2/H3K27me3 ratio. Our findings document a developmental dynamic control in the genomic distribution of H3K27me2 and H3K27me3 at regulatory regions in ESC. They also reveal that modifying the H3K27me2/H327me3 ratio is sufficient for the acquisition and repression of defined cell lineage transcriptional programs and phenotypes, along with influencing induction of the ESC ground state.
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