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RNA Polymerase II, the BAF remodeler and transcription factors synergize to evict nucleosomes

ABSTRACT: Chromatin accessibility is a hallmark of active transcription and requires ATP-dependent nucleosome remodeling by Brahma-Associated Factor (BAF). However, the mechanistic link between transcription, nucleosome remodeling, and chromatin accessibility is unclear. Here, we used a chemical-genetic approach to dissect the interplay between RNA Polymerase II (RNAPII), BAF, and DNA-sequence-specific transcription factors (TFs) in mouse embryonic stem cells. By time-resolved chromatin profiling with acute transcription block at distinct stages, we show that RNAPII promoter-proximal pausing stabilizes BAF chromatin occupancy and enhances nucleosome eviction by BAF. We find that RNAPII and BAF probe both transcriptionally active and Polycomb-repressed genomic regions and provide evidence that TFs capture transient site exposure due to nucleosome unwrapping by BAF to confer locus specificity for persistent chromatin remodeling. Our study reveals the mechanistic basis of cell-type-specific chromatin accessibility. We propose a new paradigm for how functional synergy between dynamically acting chromatin factors regulates nucleosome organization.

ORGANISM(S): Mus musculus

PROVIDER: GSE224292 | GEO | 2023/10/12

REPOSITORIES: GEO

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A structural model of the human mSWI/SNF (BAF) complex bound to the nucleosome informs disease mechanisms

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2021-02-10 | PXD020992 | Pride

Stochastic models of nucleosome dynamics reveal regulatory rules of stimulus-induced epigenome remodeling

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2024-09-30 | PXD051883 | JPOST Repository

Single-minded homolog 2 resides in the chromatin protein network of androgen receptor and modulates gene expression in prostate cancer cells Single-minded homolog 2 resides in the chromatin protein network of androgen receptor and modulates gene expression in prostate cancer cells

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2021-06-17 | PXD025193 | Pride

Pharmacologic inhibition of BAF chromatin remodeling complexes as a therapeutic approach to transcription factor-dependent cancers [PRO-seq]

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2023-09-12 | GSE241447 | GEO

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