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ChIPseq on H3K27ac, H4ac, H3K9ac, H3K4me3, H3K4me1, H3K27me3 and H2AK119Ub on TX1072 WT, Hdac3-/-, and ChIP targeting FLAG on Hdac3-AID-FLAG cell lines, at different time of Dox induction.

ABSTRACT: During development, transcriptional and chromatin modification changes co-occur but the order and causality of events often remain unclear. We explore these questions using the paradigm of X-chromosome inactivation (XCI). We initiate XCI in female, mouse embryonic stem cells by inducingXistand monitor changes in transcription and chromatin by allele-specific profiling. Our unprecedented temporal resolution identifies histone deacetylation and H2AK119 ubiquitination as the earliest chromatin alterations during XCI. Functional dissection of these changes reveals that HDAC3 is pre-bound on the X-chromosome and uponXistcoating, histone deacetylation is required for efficient gene silencing. We also reveal that PRC1-associated H2AK119Ub precedes PRC2-associated H3K27me3 during XCI. These marks accumulate initially at large, intergenic domains and then spread into genes but only in the context of gene silencing and histone deacetylation. Our results reveal a hierarchy of chromatin events at the initiation of XCI and identify their key roles in mediating transcriptional silencing.

OTHER RELATED OMICS DATASETS IN: PXD011344

ORGANISM(S): Mus musculus

PROVIDER: GSE116990 | GEO | 2019/01/01

REPOSITORIES: GEO

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