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The impact of SWI/SNF and NuRD inactivation on gene expression is tightly coupled with levels of RNA Polymerase II occupancy at promoters

ABSTRACT: SWI/SNF and NuRD are protein complexes that antagonistically regulate DNA accessibility. However, repression of their activities often leads to unanticipated changes in target gene expression (paradoxical), highlighting our incomplete understanding of their activities. Here we show that SWI/SNF and NuRD are in a tug-of-war to regulate PRC2 occupancy at lowly expressed and bivalent genes in mESCs. In contrast, at promoters of average or highly expressed genes, SWI/SNF and NuRD antagonistically modulate RNA Polymerase II release kinetics, arguably via modifying H3.3 and H2A.Z turnover rates at promoter-flanking nucleosomes, leading to paradoxical changes in gene expression. Owing to this mechanism, the relative activities of the two remodelers potentiate gene promoters towards Pol II-dependent open or PRC2-dependent closed chromatin states. Our results highlight RNA Polymerase II occupancy as the primary parameter determining the direction of gene expression changes in response to SWI/SNF and NuRD inactivation at gene promoters in mESCs.

ORGANISM(S): Mus musculus

PROVIDER: GSE206497 | GEO | 2023/01/19

REPOSITORIES: GEO

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DOC1-dependent recruitment of NURD reveals antagonism with SWI/SNF during epithelial-mesenchymal transition in oral cancer cells.

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2014-03-13 | E-GEOD-48242 | biostudies-arrayexpress

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PHF6 cooperates with SWI/SNF complexes to facilitate transcriptional progression [ChIP-seq]

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Project description:A systems understanding of nuclear organization and events is critical for determining how cells divide, differentiate and respond to stimuli and for identifying the causes of diseases. Chromatin remodeling complexes such as SWI/SNF have been implicated in a wide variety of cellular processes including gene expression, nuclear organization, centromere function and chromosomal stability, and mutations in SWI/SNF components have been linked to several types of cancer. To better understand the biological processes in which chromatin remodeling proteins participate we globally mapped binding regions for several components of the SWI/SNF complex throughout the human genome using ChIP-Seq. SWI/SNF components were found to lie near regulatory elements integral to transcription (e.g. 5M-bM-^@M-^Y ends, RNA Polymerases II and III and enhancers) as well as regions critical for chromosome organization (e.g. CTCF, lamins and DNA replication origins). To further elucidate the association of SWI/SNF subunits with each other as well as with other nuclear proteins we also analyzed SWI/SNF immunoprecipitated complexes by mass spectrometry. Individual SWI/SNF factors are associated with their own family members as well as with cellular constituents such as nuclear matrix proteins, key transcription factors and centromere components implying a ubiquitous role in gene regulation and nuclear function. We find an overrepresentation of both SWI/SNF-associated regions and proteins in cell cycle and chromosome organization. Taken together the results from our ChIP and immunoprecipitation experiments suggest that SWI/SNF facilitates gene regulation and genome function more broadly and through a greater diversity of interactions than previously appreciated. ChIP-Seq analysis of the SWI/SNF subunits Ini1, Brg1, BAF155 and BAF170 in HeLa S3 cells

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2011-03-07 | E-GEOD-24573 | biostudies-arrayexpress

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