PBRM1 bromodomains associate with RNA to facilitate chromatin association

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....

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Published in:Nucleic acids research Vol. 51; no. 8; pp. 3631 - 3649
Main Authors: De Silva, Saumya M, Dhiman, Alisha, Sood, Surbhi, Mercedes, Kilsia F, Simmons, William J, Henen, Morkos A, Vögeli, Beat, Dykhuizen, Emily C, Musselman, Catherine A
Format: Journal Article
Language:English
Published: England Oxford University Press 08.05.2023
Subjects:
Chromatin - genetics
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
Gene regulation, Chromatin and Epigenetics
Histones - metabolism
Humans
Kidney Neoplasms - genetics
Nuclear Proteins - metabolism
RNA - genetics
Transcription Factors - metabolism
ISSN:0305-1048, 1362-4962, 1362-4962
Online Access:Get full text
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Summary: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.
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The authors wish it to be known that, in their opinion, the first two authors should be regarded as Joint First Authors.
ISSN:0305-1048
1362-4962
1362-4962
DOI:10.1093/nar/gkad072