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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| Veröffentlicht in: | Nucleic acids research 2023-05, Vol.51 (8), p.3631-3649 |
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| container_title | Nucleic acids research |
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| creator | 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 |
| description | 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. |
| doi_str_mv | 10.1093/nar/gkad072 |
| format | Article |
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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.</description><identifier>ISSN: 0305-1048</identifier><identifier>ISSN: 1362-4962</identifier><identifier>EISSN: 1362-4962</identifier><identifier>DOI: 10.1093/nar/gkad072</identifier><identifier>PMID: 36808431</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>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</subject><ispartof>Nucleic acids research, 2023-05, Vol.51 (8), p.3631-3649</ispartof><rights>The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research. 2023</rights><rights>The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c413t-9962c783e958bb3c720a1371ecd912cdbcc7db95ba94489fa27651afbb1998f23</citedby><cites>FETCH-LOGICAL-c413t-9962c783e958bb3c720a1371ecd912cdbcc7db95ba94489fa27651afbb1998f23</cites><orcidid>0000-0003-4835-5583 ; 0000-0003-3072-1469 ; 0000-0002-8356-7971 ; 0000-0003-1176-3137</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10164552/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10164552/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,1603,27923,27924,53790,53792</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36808431$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>De Silva, Saumya M</creatorcontrib><creatorcontrib>Dhiman, Alisha</creatorcontrib><creatorcontrib>Sood, Surbhi</creatorcontrib><creatorcontrib>Mercedes, Kilsia F</creatorcontrib><creatorcontrib>Simmons, William J</creatorcontrib><creatorcontrib>Henen, Morkos A</creatorcontrib><creatorcontrib>Vögeli, Beat</creatorcontrib><creatorcontrib>Dykhuizen, Emily C</creatorcontrib><creatorcontrib>Musselman, Catherine A</creatorcontrib><title>PBRM1 bromodomains associate with RNA to facilitate chromatin association</title><title>Nucleic acids research</title><addtitle>Nucleic Acids Res</addtitle><description>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.</description><subject>Chromatin - genetics</subject><subject>DNA-Binding Proteins - genetics</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Gene regulation, Chromatin and Epigenetics</subject><subject>Histones - metabolism</subject><subject>Humans</subject><subject>Kidney Neoplasms - genetics</subject><subject>Nuclear Proteins - metabolism</subject><subject>RNA - genetics</subject><subject>Transcription Factors - metabolism</subject><issn>0305-1048</issn><issn>1362-4962</issn><issn>1362-4962</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>TOX</sourceid><sourceid>EIF</sourceid><recordid>eNp9kF1LwzAUhoMobk6vvJdeiSDVnCZtkiuZw4-BXwy9DkmabtG2mU2n-O_t2Bx649WBcx7e8_IgdAj4DLAg57VqzqdvKscs2UJ9IFkSU5El26iPCU5jwJT30F4IrxgDhZTuoh7JOOaUQB-Nny4n9xDpxlc-95VydYhUCN441dro07WzaPIwjFofFcq40rXLtZl1uGpdvUGdr_fRTqHKYA_Wc4Berq-eR7fx3ePNeDS8iw0F0saiq2YYJ1akXGtiWIIVEAbW5AISk2tjWK5FqpWglItCJSxLQRVagxC8SMgAXaxy5wtd2dzYum1UKeeNq1TzJb1y8u-ldjM59R8SMGQ0TZcJJ-uExr8vbGhl5YKxZalq6xdBJoxxwUiGeYeerlDT-BAaW2z-AJZL-7KzL9f2O_rod7UN-6O7A45XgF_M_036BvySj4Y</recordid><startdate>20230508</startdate><enddate>20230508</enddate><creator>De Silva, Saumya M</creator><creator>Dhiman, Alisha</creator><creator>Sood, Surbhi</creator><creator>Mercedes, Kilsia F</creator><creator>Simmons, William J</creator><creator>Henen, Morkos A</creator><creator>Vögeli, Beat</creator><creator>Dykhuizen, Emily C</creator><creator>Musselman, Catherine A</creator><general>Oxford University Press</general><scope>TOX</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-4835-5583</orcidid><orcidid>https://orcid.org/0000-0003-3072-1469</orcidid><orcidid>https://orcid.org/0000-0002-8356-7971</orcidid><orcidid>https://orcid.org/0000-0003-1176-3137</orcidid></search><sort><creationdate>20230508</creationdate><title>PBRM1 bromodomains associate with RNA to facilitate chromatin association</title><author>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</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c413t-9962c783e958bb3c720a1371ecd912cdbcc7db95ba94489fa27651afbb1998f23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Chromatin - genetics</topic><topic>DNA-Binding Proteins - genetics</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>Gene regulation, Chromatin and Epigenetics</topic><topic>Histones - metabolism</topic><topic>Humans</topic><topic>Kidney Neoplasms - genetics</topic><topic>Nuclear Proteins - metabolism</topic><topic>RNA - genetics</topic><topic>Transcription Factors - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>De Silva, Saumya M</creatorcontrib><creatorcontrib>Dhiman, Alisha</creatorcontrib><creatorcontrib>Sood, Surbhi</creatorcontrib><creatorcontrib>Mercedes, Kilsia F</creatorcontrib><creatorcontrib>Simmons, William J</creatorcontrib><creatorcontrib>Henen, Morkos A</creatorcontrib><creatorcontrib>Vögeli, Beat</creatorcontrib><creatorcontrib>Dykhuizen, Emily C</creatorcontrib><creatorcontrib>Musselman, Catherine A</creatorcontrib><collection>Oxford Journals Open Access Collection</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Nucleic acids research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>De Silva, Saumya M</au><au>Dhiman, Alisha</au><au>Sood, Surbhi</au><au>Mercedes, Kilsia F</au><au>Simmons, William J</au><au>Henen, Morkos A</au><au>Vögeli, Beat</au><au>Dykhuizen, Emily C</au><au>Musselman, Catherine A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>PBRM1 bromodomains associate with RNA to facilitate chromatin association</atitle><jtitle>Nucleic acids research</jtitle><addtitle>Nucleic Acids Res</addtitle><date>2023-05-08</date><risdate>2023</risdate><volume>51</volume><issue>8</issue><spage>3631</spage><epage>3649</epage><pages>3631-3649</pages><issn>0305-1048</issn><issn>1362-4962</issn><eissn>1362-4962</eissn><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.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>36808431</pmid><doi>10.1093/nar/gkad072</doi><tpages>19</tpages><orcidid>https://orcid.org/0000-0003-4835-5583</orcidid><orcidid>https://orcid.org/0000-0003-3072-1469</orcidid><orcidid>https://orcid.org/0000-0002-8356-7971</orcidid><orcidid>https://orcid.org/0000-0003-1176-3137</orcidid><oa>free_for_read</oa></addata></record> |
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| 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 |
| title | PBRM1 bromodomains associate with RNA to facilitate chromatin association |
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