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

被引：22

作者：

Blumli, Seraina ^{[1
,7
]}

Wiechens, Nicola ^{[1
]}

Wu, Meng-Ying ^{[1
,8
]}

Singh, Vijender ^{[2
]}

Gierlinski, Marek ^{[3
]}

Schweikert, Gabriele ^{[3
]}

Gilbert, Nick ^{[4
]}

Naughton, Catherine ^{[5
]}

Sundaramoorthy, Ramasubramanian ^{[1
]}

Varghese, Joby ^{[5
]}

Gourlay, Robert ^{[5
]}

Soares, Renata ^{[5
]}

Clark, David ^{[6
]}

Owen-Hughes, Tom ^{[1
]}

机构：

[1] Univ Dundee, Ctr Gene Regulat & Express, Sch Life Sci, Dundee DD1 5EH, Scotland

[2] Univ Connecticut, Computat Core, 67 North Eagleville Rd, Storrs, CT 06269 USA

[3] Univ Dundee, Sch Life Sci, Computat Biol, Dundee DD1 5EH, Scotland

[4] Univ Edinburgh, Inst Genet & Canc, MRC Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland

[5] Univ Dundee, MRC Prot Phosphorylat & Ubiquitylat Unit, Dundee DD1 5EH, Scotland

[6] NICHHD, Div Dev Biol, NIH, Bldg 6A,6 Ctr Dr, Bethesda, MD 20892 USA

[7] AstraZeneca, R&D, Antibody Discovery & Prot Engn ADPE, Granta Pk, Cambridge CB21 6GH, England

[8] Kings Coll London, James Black Ctr, Sch Cardiovasc Med & Sci, Denmark Hill, London SE5 9NU, England

来源：

CELL REPORTS | 2021年 / 37卷 / 05期

关键词：

DIFFERENTIAL EXPRESSION ANALYSIS; GENOME-WIDE; FREQUENT MUTATIONS; SUPER-ENHANCERS; GENE-EXPRESSION; CELL IDENTITY; CHROMATIN; PLURIPOTENCY; BINDING; DNA;

D O I：

10.1016/j.celrep.2021.109943

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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 co activator 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.

引用

页数：26

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