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Genome-wide analysis of effects of ARID1A depletion in mouse embryonic stem cells

ABSTRACT: A degron system is used to deplete ARID1A a subunit of the SWI/SNF complex in mouse embryonic stem cells. Genome wide analysis of chromatin accessibility (ATAC-seq), nucleosome posistioning (MNase-seq), nascent transcription (TT-seq), binding to EP300 and presence of histone H3 K27acetylation (ChIP-seq) amd histone H3K27 tria-methylation (ChIP-seq) allowed us to identify two different pathways responsible for the up and downregulation of transcription following the loss of ARID1A. The rapid depletion of ARID1A generates mini domains of nucleomes at pluripotency transcription factor binding sites. Loss of ARID1A also results in the redistribution of the co-activator EP300. Locations of co-incident EP300 dissociation and lost chromatin accessibility occur adjacent to rapidly downregulated genes. Promoter proximal regions that gain EP300 are linked to genes that are transcriptionally upregulated. Our findings illustrate the importance of both direct and indirect effects in causing rapid changes to gene expression. Only a few genes are directly affected after ARID1A depletion and contribute to pathways associated with cancer and pluripotency establishing the loss of ARID1A phenotype.

ORGANISM(S): Mus musculus

PROVIDER: GSE183278 | GEO | 2021/10/24

REPOSITORIES: GEO

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