Association of BRCA1 with the inactive X chromosome and XIST RNA

Shridar Ganesan, Daniel P. Silver, Ronny Drapkin, Roger Greenberg, Jean Feunteun, David M. Livingston

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33 Scopus citations


Breast cancer, early onset 1 (BRCA1) encodes a nuclear protein that participates in breast and ovarian cancer suppression. The molecular basis for the gender and tissue specificity of the BRCA1 cancer syndrome is unknown. Recently, we observed that a fraction of BRCA1 in female cells is localized on the inactive X chromosome (Xi). Chromatin immunoprecipitation (ChIP) experiments have demonstrated that BRCA1 physically associates with Xi-specific transcript (XIST) RNA, a non-coding RNA known to coat Xi and to participate in the initiation of its inactivation during early embryogenesis. Cells lacking wild-type BRCA1 show abnormalities in Xi, including lack of proper XIST RNA localization. Reintroduction of wild-type, but not mutant, BRCA1 can correct this defect in XIST localization in these cells. Depletion of BRCA1 in female diploid cells led to a defect in proper XIST localization on Xi and in the development of normal Xi heterchromatic superstructure. Moreover, depletion of BRCA1 led to an increased likelihood of re-expression of a green fluorescent protein (GFP) reporter gene embedded on Xi. Taken together, these findings are consistent with a model in which BRCA1 function contributes to the maintenance of proper Xi heterochromatin superstructure. Although the data imply a novel gender-specific consequence of BRCA1 loss, the relevance of the BRCA1/Xi function to the tumour suppressor activity of BRCA1 remains unclear and needs to be tested.

Original languageEnglish (US)
Pages (from-to)123-128
Number of pages6
JournalPhilosophical Transactions of the Royal Society B: Biological Sciences
Issue number1441
StatePublished - Jan 29 2004
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)


  • BRCA1
  • Breast cancer
  • Heterochromatin
  • X chromosome inactivation
  • XIST


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