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

Seraina Blümli | Zendy; Nicola Wiechens | Zendy; Mengying Wu | Zendy; Vijender Singh | Zendy; Marek Gierliński | Zendy; Gabriele Schweikert | Zendy; Nick Gilbert | Zendy; Catherine Naughton | Zendy; Ramasubramanian Sundaramoorthy | Zendy; Joby Varghese | Zendy; Robert Gourlay | Zendy; Renata Soares | Zendy; David J. Clark | Zendy; Tom OwenHughes | Zendy

Open Access

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

Author(s) -

Seraina Blümli,

Nicola Wiechens,

Mengying Wu,

Vijender Singh,

Marek Gierliński,

Gabriele Schweikert,

Nick Gilbert,

Catherine Naughton,

Ramasubramanian Sundaramoorthy,

Joby Varghese,

Robert Gourlay,

Renata Soares,

David J. Clark,

Tom OwenHughes

Publication year - 2021

Publication title -

cell reports

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 6.264

H-Index - 154

eISSN - 2639-1856

pISSN - 2211-1247

DOI - 10.1016/j.celrep.2021.109943

Subject(s) - psychological repression , swi/snf , arid1a , protein subunit , transcription (linguistics) , microbiology and biotechnology , transcription factor , chemistry , biology , genetics , gene , chromatin remodeling , gene expression , mutation , linguistics , philosophy

Summary 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.

The content you want is available to Zendy users.

Already have an account? Click here to sign in.

Having issues? You can contact us here

Accelerating Research