BRCA1 supports XIST RNA concentration on the inactive X chromosome

Cell. 2002 Nov 1;111(3):393-405. doi: 10.1016/s0092-8674(02)01052-8.

Shridar Ganesan ¹, 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

Affiliations

Affiliation

1 The Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.

PMID: 12419249 DOI: 10.1016/s0092-8674(02)01052-8

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.

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