Cholesterol is required for transcriptional repression by BASP1

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dc.contributor.authorLoats, Amy E.en
dc.contributor.authorCarrera, Samanthaen
dc.contributor.authorFleming, Anna F.en
dc.contributor.authorRoberts, Abigail R. E.en
dc.contributor.authorSherrard, Aliceen
dc.contributor.authorToska, Enedaen
dc.contributor.authorMoorhouse, Alexander J.en
dc.contributor.authorMedler, Kathryn F.en
dc.contributor.authorRoberts, Stefan G. E.en
dc.date.accessioned2025-01-10T15:53:42Zen
dc.date.available2025-01-10T15:53:42Zen
dc.date.issued2021-07-15en
dc.description.abstractLipids are present within the cell nucleus, where they engage with factors involved in gene regulation. Cholesterol associates with chromatin in vivo and stimulates nucleosome packing in vitro, but its effects on specific transcriptional responses are not clear. Here, we show that the lipidated Wilms tumor 1 (WT1) transcriptional corepressor, brain acid soluble protein 1 (BASP1), interacts with cholesterol in the cell nucleus through a conserved cholesterol interaction motif. We demonstrate that BASP1 directly recruits cholesterol to the promoter region of WT1 target genes. Mutation of BASP1 to ablate its interaction with cholesterol or the treatment of cells with drugs that block cholesterol biosynthesis inhibits the transcriptional repressor function of BASP1. We find that the BASP1–cholesterol interaction is required for BASP1-dependent chromatin remodeling and the direction of transcription programs that control cell differentiation. Our study uncovers a mechanism for gene-specific targeting of cholesterol where it is required to mediate transcriptional repression.en
dc.description.versionPublished versionen
dc.format.extent11 page(s)en
dc.format.mimetypeapplication/pdfen
dc.identifierARTN e2101671118 (Article number)en
dc.identifier.doihttps://doi.org/10.1073/pnas.2101671118en
dc.identifier.eissn1091-6490en
dc.identifier.issn0027-8424en
dc.identifier.issue29en
dc.identifier.orcidRoberts, Stefan [0000-0002-7535-6365]en
dc.identifier.orcidMedler, Kathryn [0000-0001-9664-3606]en
dc.identifier.other2101671118 (PII)en
dc.identifier.pmid34266955en
dc.identifier.urihttps://hdl.handle.net/10919/124131en
dc.identifier.volume118en
dc.language.isoenen
dc.publisherNational Academy of Sciencesen
dc.relation.urihttps://www.ncbi.nlm.nih.gov/pubmed/34266955en
dc.rightsCreative Commons Attribution-NonCommercial-NoDerivatives 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en
dc.subjectBASP1en
dc.subjectWT1en
dc.subjectcholesterolen
dc.subjecttranscriptionen
dc.subjectchromatinen
dc.subject.meshK562 Cellsen
dc.subject.meshCell Nucleusen
dc.subject.meshHumansen
dc.subject.meshCholesterolen
dc.subject.meshMembrane Proteinsen
dc.subject.meshNerve Tissue Proteinsen
dc.subject.meshRepressor Proteinsen
dc.subject.meshTranscription, Geneticen
dc.subject.meshDown-Regulationen
dc.subject.meshProtein Bindingen
dc.subject.meshPromoter Regions, Geneticen
dc.titleCholesterol is required for transcriptional repression by BASP1en
dc.title.serialProceedings of the National Academy of Sciences of the United States of Americaen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.otherArticleen
dc.type.otherJournalen
pubs.organisational-groupVirginia Techen
pubs.organisational-groupVirginia Tech/Agriculture & Life Sciencesen
pubs.organisational-groupVirginia Tech/Agriculture & Life Sciences/School of Animal Sciencesen
pubs.organisational-groupVirginia Tech/Agriculture & Life Sciences/Biochemistryen
pubs.organisational-groupVirginia Tech/All T&R Facultyen
pubs.organisational-groupVirginia Tech/Agriculture & Life Sciences/CALS T&R Facultyen

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