PBRM1 bromodomains associate with RNA to facilitate chromatin association-Reference-Cited by-同舟云学术

PBRM1 bromodomains associate with RNA to facilitate chromatin association

Published:2023-02-20 Issue:8 Volume:51 Page:3631-3649
ISSN:0305-1048
Container-title:Nucleic Acids Research
language:en
Short-container-title:

Author:

De Silva Saumya M¹²,Dhiman Alisha³,Sood Surbhi³,Mercedes Kilsia F¹,Simmons William J¹,Henen Morkos A¹^ORCID,Vögeli Beat¹^ORCID,Dykhuizen Emily C³^ORCID,Musselman Catherine A¹²^ORCID

Affiliation:

1. Department of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus , Aurora , CO 80045, USA

2. Department of Biochemistry, University of Iowa , Iowa City, IA 52242, USA

3. Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University , West Lafayette , IN 47907, USA

Abstract

Abstract PBRM1 is a subunit of the PBAF chromatin remodeling complex, which is mutated in 40–50% of clear cell renal cell carcinoma patients. It is thought to largely function as a chromatin binding subunit of the PBAF complex, but the molecular mechanism underlying this activity is not fully known. PBRM1 contains six tandem bromodomains which are known to cooperate in binding of nucleosomes acetylated at histone H3 lysine 14 (H3K14ac). Here, we demonstrate that the second and fourth bromodomains from PBRM1 also bind nucleic acids, selectively associating with double stranded RNA elements. Disruption of the RNA binding pocket is found to compromise PBRM1 chromatin binding and inhibit PBRM1-mediated cellular growth effects.

Funder

Holden Comprehensive Cancer Center

University of Iowa

National Cancer Institute

NIH

College of Pharmacy

Graduate College

Publisher

Oxford University Press (OUP)

Subject

Genetics

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