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H3K27me3 shapes DNA methylome by inhibiting UHRF1-mediated H3 ubiquitination

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE159043 | GEO | 2022/06/27

REPOSITORIES: GEO

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H3K27me3 shapes DNA methylome by inhibiting UHRF1-mediated H3 ubiquitination [ChIP-seq]

Project description:DNA methylation and histone lysine tri-methylation at H3K27 (H3K27me3) are the two primary epigenetic marks for transcriptional silencing essential for cell fate determination and cell lineage commitment during development1, 2. These two marks are mutually exclusive and target distinct sets of genes in the mammalian genome3. However, whether and how H3K27me3 shapes the DNA methylome remains unknown. Here, we report that the loss of H3K27me3 modification leads to increased DNA methylation at previously marked H3K27me3 sites, revealing that H3K27me3 negatively regulates DNA methylation. Genome-wide analysis of H3 ubiquitination, essential for recruitment and activation of DNA methyltransferase DNMT14, reveals the absence of H3 ubiquitination at H3K27me3 marked nucleosomes. Moreover, loss of H3K27me3 modification induces an increase in H3K18 ubiquitination at the corresponding hypermethylated loci. Importantly, we show that H3K27me3 directly inhibits UHRF1-mediated H3 ubiquitination toward nucleosomes in a defined biochemical assay. Furthermore, UHRF1 is required for the increase in DNA methylation at previously marked H3K27me3 sites in cells with abolished H3K27me3 modification. Taken together, our findings reveal a general mechanism for H3K27me3-mediated shaping of the mammalian DNA methylome via modulation of H3 ubiquitination.

2022-06-27 | GSE159042 | GEO

H3K27me3 shapes DNA methylome by inhibiting UHRF1-mediated H3 ubiquitination [RNA-seq]

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H3K27me3 shapes DNA methylome by inhibiting UHRF1-mediated H3 ubiquitination [Bisulfite-seq]

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H3K27me3 shapes DNA methylome by inhibiting UHRF1-mediated H3 ubiquitination

Project description:H3K27me3 shapes DNA methylome by inhibiting UHRF1-mediated H3 ubiquitination

| PRJNA667466 | ENA

H3K27me3 shapes DNA methylome by inhibiting UHRF1-mediated H3 ubiquitination [RNA-seq]

Project description:H3K27me3 shapes DNA methylome by inhibiting UHRF1-mediated H3 ubiquitination [RNA-seq]

| PRJNA667471 | ENA

H3K27me3 shapes DNA methylome by inhibiting UHRF1-mediated H3 ubiquitination [ChIP-seq]