title: BRCA1 supports XIST RNA concentration on the inactive X chromosome.
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.
authors.affiliation: The Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Shridar
authors.initials: S
authors.lastname: Ganesan
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Silver
authors.forename: Roger A
authors.initials: RA
authors.lastname: Greenberg
authors.forename: Dror
authors.initials: D
authors.lastname: Avni
authors.forename: Ronny
authors.initials: R
authors.lastname: Drapkin
authors.forename: Alexander
authors.initials: A
authors.lastname: Miron
authors.forename: Samuel C
authors.initials: SC
authors.lastname: Mok
authors.forename: Voahangy
authors.initials: V
authors.lastname: Randrianarison
authors.forename: Steven
authors.initials: S
authors.lastname: Brodie
authors.forename: Jennifer
authors.initials: J
authors.lastname: Salstrom
authors.forename: Theodore P
authors.initials: TP
authors.lastname: Rasmussen
authors.forename: Ann
authors.initials: A
authors.lastname: Klimke
authors.forename: Christine
authors.initials: C
authors.lastname: Marrese
authors.forename: York
authors.initials: Y
authors.lastname: Marahrens
authors.forename: Chu Xia
authors.initials: CX
authors.lastname: Deng
authors.forename: Jean
authors.initials: J
authors.lastname: Feunteun
authors.forename: David M
authors.initials: DM
authors.lastname: Livingston
mesh_terms: D000818:Animals; D019313:BRCA1 Protein / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D019175:DNA Methylation; D004303:Dosage Compensation, Genetic; D005260:Female; D015870:Gene Expression; D006657:Histones / Q000378:metabolism; D006801:Humans; D008239:Lysine / Q000378:metabolism; D008297:Male; D051379:Mice; D012313:RNA / Q000378:metabolism*; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D013090:Spermatocytes / Q000378:metabolism; D013194:Staining and Labeling / Q000379:methods; D014157:Transcription Factors / Q000235:genetics*; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D014960:X Chromosome / Q000378:metabolism*
chemical_list: D019313:BRCA1 Protein; D002352:Carrier Proteins; D006657:Histones; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C077885:XIST non-coding RNA; D012313:RNA; C102449:BARD1 protein, human; C491163:Bard1 protein, mouse; D044767:Ubiquitin-Protein Ligases; D008239:Lysine