BRCA1 supports XIST RNA concentration on the inactive X chromosome

被引：234

作者：

Ganesan, S

Silver, DP

Greenberg, RA

Avni, D

Drapkin, R

Miron, A

Mok, SC

Randrianarison, V

Brodie, S

Salstrom, J

Rasmussen, TP

Klimke, A

Marrese, C

Marahrens, Y

Deng, CX

Feunteun, J

Livingston, DM

机构：

[1] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA

[2] Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Lab Gynecol Oncol, Boston, MA 02115 USA

[3] Inst Gustave Roussy, Lab Genet Oncol, Lab Vectorol & Transfert Genes, F-94805 Villejuif, France

[4] NIDDKD, Genet Dev & Dis Branch 10 9N105, NIH, Bethesda, MD 20892 USA

[5] Univ Calif Los Angeles, Dept Human Genet, Gonda Ctr, Los Angeles, CA 90095 USA

[6] Univ Connecticut, Ctr Regenerat Biol, Storrs, CT 06269 USA

[7] Univ Connecticut, Dept Anim Sci, Storrs, CT 06269 USA

来源：

CELL | 2002年 / 111卷 / 03期

关键词：

D O I：

10.1016/S0092-8674(02)01052-8

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：393 / 405

页数：13

共 52 条

[1] Xist RNA is associated with the transcriptionally inactive XY body in mammalian male meiosis [J].