The XIST Noncoding RNA Functions Independently of BRCA1 in X Inactivation

Cuiying Xiao, Judith A. Sharp, Misako Kawahara, Albert R. Davalos, Michael J. Difilippantonio, Ying Hu, Wenmei Li, Liu Cao, Ken Buetow, Thomas Ried, Brian P. Chadwick, Chu Xia Deng, Barbara Panning

Research output: Contribution to journalLetterpeer-review

64 Scopus citations

Abstract

Females with germline mutations in BRCA1 are predisposed to develop breast and ovarian cancers. A previous report indicated that BRCA1 colocalizes with and is necessary for the correct localization of XIST, a noncoding RNA that coats the inactive X chromosome (Xi) to mediate formation of facultative heterochromatin. A model emerged from this study suggesting that loss of BRCA1 in female cells could reactivate genes on the Xi through loss of the XIST RNA. However, our independent studies of BRCA1 and XIST RNA revealed little evidence to support this model. We report that BRCA1 is not enriched on XIST RNA-coated chromatin of the Xi. Neither mutation nor depletion of BRCA1 causes significant changes in XIST RNA localization or X-linked gene expression. Together, these results do not support a role for BRCA1 in promoting XIST RNA localization to the Xi or regulating XIST-dependent functions in maintaining the stability of facultative heterochromatin.

Original languageEnglish (US)
Pages (from-to)977-989
Number of pages13
JournalCell
Volume128
Issue number5
DOIs
StatePublished - Mar 9 2007
Externally publishedYes

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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