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Acute depletion of the ARID1A subunit of SWI/SNF complexes reveals distinct pathways for activation and repression of transcription

Year: 2021
Type: article
Abstract: The ARID1A subunit of SWI/SNF chromatin remodeling complexes is a potent tumor suppressor. Here, a degron is applied to detect rapid loss of chromatin accessibility at thousands of loci where ARID1A acts to generate accessible minidomains of nucleosomes. Loss of ARID1A also results in the redistribution of the coactivator EP300. Co-incident EP300 dissociation and lost chromatin accessibility at enhancer elements are highly enriched adjacent to rapidly downregulated genes. In contrast, sites of gained EP300 occupancy are linked to genes that are transcriptionally upregulated. These chromatin changes are associated with a small number of genes that are differentially expressed in the first hours following loss of ARID1A. Indirect or adaptive changes dominate the transcriptome following growth for days after loss of ARID1A and result in strong engagement with cancer pathways. The identification of this hierarchy suggests sites for intervention in ARID1A-driven diseases.
Source: Cell Reports
DOI: 10.1016/j.celrep.2021.109943
Authors: Seraina Blümli, Nicola Wiechens, Meng-Ying Wu, Vijender Singh, Marek Gierlinski, Gabriele Schweikert, Nick Gilbert, Catherine Naughton, Ramasubramanian Sundaramoorthy, Joby Varghese, Robert Gourlay, Renata Soares, David Clark, Tom Owen-Hughes
Institutions: University of Dundee, University of Connecticut, Institute of Genetics and Cancer, MRC Human Genetics Unit, University of Edinburgh, MRC Protein Phosphorylation and Ubiquitylation Unit, National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Language: English
Open Access status: gold
Estimated APC paid: $5,200
OpenAlex ID: W3208197345
FWCI: 2.237
Cites: 109
Cited by: 53
Related to: 10