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Cell-type-specific epigenomic variations associated with BRCA1 mutation in pre-cancer human breast tissues

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dc.contributor.authorHsieh, Yuan-Pangen
dc.contributor.authorNaler, Lynette B.en
dc.contributor.authorMa, Saien
dc.contributor.authorLu, Changen
dc.date.accessioned2022-08-05T18:07:54Zen
dc.date.available2022-08-05T18:07:54Zen
dc.date.issued2022-01-13en
dc.description.abstractBRCA1 germline mutation carriers are predisposed to breast cancers. Epigenomic regulations have been known to strongly interact with genetic variations and potentially mediate biochemical cascades involved in tumorigenesis. Due to the cell-type specificity of epigenomic features, profiling of individual cell types is critical for understanding the molecular events in various cellular compartments within complex breast tissue. Here, we produced cell-type-specific profiles of genome-wide histone modifications including H3K27ac and H3K4me3 in basal, luminal progenitor, mature luminal and stromal cells extracted from a small pilot cohort of pre-cancer BRCA1 mutation carriers (BRCA1(mut/+)) and non-carriers (BRCA1(+/+)), using a low-input ChIP-seq technology that we developed. We discovered that basal and stromal cells present the most extensive epigenomic differences between mutation carriers (BRCA1(mut/+)) and non-carriers (BRCA1(+/+)), while luminal progenitor and mature luminal cells are relatively unchanged with the mutation. Furthermore, the epigenomic changes in basal cells due to BRCA1 mutation appear to facilitate their transformation into luminal progenitor cells. Taken together, epigenomic regulation plays an important role in the case of BRCA1 mutation for shaping the molecular landscape that facilitates tumorigenesis.en
dc.description.notesNational Institutes of Health (NIH) [R33 CA214176, R01 CA243249, P30 CA012197 to C.L.]; Virginia Tech Institute for Critical Technology and Applied Science (to C.L.). Funding for open access charge: Virginia Tech foundation grant.en
dc.description.sponsorshipNational Institutes of Health (NIH) [R33 CA214176, R01 CA243249, P30 CA012197]; Virginia Tech Institute for Critical Technology and Applied Science; Virginia Tech foundation granten
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1093/nargab/lqac006en
dc.identifier.eissn2631-9268en
dc.identifier.issue1en
dc.identifier.otherlqac006en
dc.identifier.pmid35118379en
dc.identifier.urihttp://hdl.handle.net/10919/111479en
dc.identifier.volume4en
dc.language.isoenen
dc.publisherOxford University Pressen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectepithelial-mesenchymal transitionen
dc.subjectmammary-glanden
dc.subjectepigenetic regulationen
dc.subjectovarian-canceren
dc.subjectdna-bindingen
dc.subjectexpressionen
dc.subjectgeneen
dc.subjecttranscriptionen
dc.subjectchromatinen
dc.subjectphenotypeen
dc.titleCell-type-specific epigenomic variations associated with BRCA1 mutation in pre-cancer human breast tissuesen
dc.title.serialNar Genomics and Bioinformaticsen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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