BRCA1 supports XIST RNA concentration on the inactive X chromosome

Shridar Ganesan, Daniel P. Silver, Roger A. Greenberg, Dror Avni, Ronny Drapkin, Alexander Miron, Samuel C. Mok, Voahangy Randrianarison, Steven Brodie, Jennifer Salstrom, Theodore P. Rasmussen, Ann Klimke, Christine Marrese, York Marahrens, Chu Xia Deng, Jean Feunteun, David M. Livingston*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

BRCA1, a breast and ovarian tumor suppressor, colocalizes with markers of the inactive X chromosome (Xi) on Xi in female somatic cells and associates with XIST RNA, as detected by chromatin immunoprecipitation. Breast and ovarian carcinoma cells lacking BRCA1 show evidence of defects in Xi chromatin structure. Reconstitution of BRCA1-deficient cells with wt BRCA1 led to the appearance of focal XIST RNA staining without altering XIST abundance. Inhibiting BRCA1 synthesis in a suitable reporter line led to increased expression of an otherwise silenced Xi-located GFP transgene. These observations suggest that loss of BRCA1 in female cells may lead to Xi perturbation and destabilization of its silenced state.

Original languageEnglish
Pages (from-to)393-405
Number of pages13
JournalCell
Volume111
Issue number3
DOIs
StatePublished - 1 Nov 2002
Externally publishedYes

Funding

FundersFunder number
Howard Hughes Medical Institute
National Cancer Institute
National Institute of Diabetes and Digestive and Kidney DiseasesZIADK056001
Appalachian Regional Commission
Dana-Farber Cancer Institute

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