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dc.contributor.authorPageau, Gayle Jeannette
dc.contributor.authorHall, Lisa L.
dc.contributor.authorLawrence, Jeanne B.
dc.date2022-08-11T08:08:47.000
dc.date.accessioned2022-08-23T16:08:21Z
dc.date.available2022-08-23T16:08:21Z
dc.date.issued2007-03-06
dc.date.submitted2009-09-14
dc.identifier.issn0730-2312 (Print)
dc.identifier.pmid17146760
dc.identifier.urihttp://hdl.handle.net/20.500.14038/32426
dc.description.abstractThe BRCA1 tumor suppressor involved in breast and ovarian cancer is linked to several fundamental cell regulatory processes. Recently, it was reported that BRCA1 supports localization of XIST RNA to the inactive X chromosome (Xi) in women. The apparent cytological overlap between BRCA1 and XIST RNA across the Xi raised the possibility a direct role of BRCA1 in localizing XIST. We report here that BRCA1 does not paint the Xi or XIST territory, as do markers of Xi facultative heterochromatin. A smaller BRCA1 accumulation abuts Xi, although this is not exclusive to Xi. In BRCA1 depleted normal and tumor cells, or BRCA1 reconstituted cells, BRCA1 status does not closely correlate with XIST localization, however in a BRCA1 inducible system over-expression correlated strongly with enhanced XIST expression. We confirm frequent loss of an Xi in tumor cells. In addition to mitotic loss of Xi, we find XIST RNA expression or localization frequently become compromised in cultured breast cancer cells, suggesting Xi heterochromatin may not be fully maintained. We demonstrate that complex epigenetic differences between tumor cell subpopulations can have striking effects on XIST transcription, accumulation, and localization, but this does not strictly correlate with BRCA1. Although BRCA1 can have indirect effects that impact XIST, our results do not indicate a direct and specific role in XIST RNA regulation. Rather, regulatory factors such as BRCA1 that have broad effects on chromatin or gene regulation can impact XIST RNA and the Xi. We provide preliminary evidence that this may occur as part of a wider failure of heterochromatin maintenance in some cancers.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=17146760&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.1002/jcb.21188
dc.rightsCitation: J Cell Biochem. 2007 Mar 1;100(4):835-50. <a href="http://dx.doi.org/10.1002/jcb.21188">Link to article on publisher's site</a>
dc.subjectBRCA1 Protein
dc.subjectBreast Neoplasms
dc.subjectCell Line
dc.subjectCell Line, Tumor
dc.subjectChromosomes, Human, X
dc.subjectFemale
dc.subjectHeterochromatin
dc.subjectHumans
dc.subjectIn Situ Hybridization, Fluorescence
dc.subjectRNA Interference
dc.subjectRNA, Untranslated
dc.subjectX Chromosome Inactivation
dc.subjectCell Biology
dc.titleBRCA1 does not paint the inactive X to localize XIST RNA but may contribute to broad changes in cancer that impact XIST and Xi heterochromatin
dc.typeJournal Article
dc.source.journaltitleJournal of cellular biochemistry
dc.source.volume100
dc.source.issue4
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/gsbs_mdphd/9
dc.identifier.contextkey1004108
html.description.abstract<p>The BRCA1 tumor suppressor involved in breast and ovarian cancer is linked to several fundamental cell regulatory processes. Recently, it was reported that BRCA1 supports localization of XIST RNA to the inactive X chromosome (Xi) in women. The apparent cytological overlap between BRCA1 and XIST RNA across the Xi raised the possibility a direct role of BRCA1 in localizing XIST. We report here that BRCA1 does not paint the Xi or XIST territory, as do markers of Xi facultative heterochromatin. A smaller BRCA1 accumulation abuts Xi, although this is not exclusive to Xi. In BRCA1 depleted normal and tumor cells, or BRCA1 reconstituted cells, BRCA1 status does not closely correlate with XIST localization, however in a BRCA1 inducible system over-expression correlated strongly with enhanced XIST expression. We confirm frequent loss of an Xi in tumor cells. In addition to mitotic loss of Xi, we find XIST RNA expression or localization frequently become compromised in cultured breast cancer cells, suggesting Xi heterochromatin may not be fully maintained. We demonstrate that complex epigenetic differences between tumor cell subpopulations can have striking effects on XIST transcription, accumulation, and localization, but this does not strictly correlate with BRCA1. Although BRCA1 can have indirect effects that impact XIST, our results do not indicate a direct and specific role in XIST RNA regulation. Rather, regulatory factors such as BRCA1 that have broad effects on chromatin or gene regulation can impact XIST RNA and the Xi. We provide preliminary evidence that this may occur as part of a wider failure of heterochromatin maintenance in some cancers.</p>
dc.identifier.submissionpathgsbs_mdphd/9
dc.contributor.departmentGraduate School of Biomedical Sciences, MD/PhD Program
dc.contributor.departmentDepartment of Cell Biology
dc.source.pages835-50
dc.contributor.studentGayle Pageau


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