BRCA1 supports XIST RNA concentration on the inactive X chromosome.
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.
Ganesan
Shridar
S
The Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Silver
Daniel P
DP
Greenberg
Roger A
RA
Avni
Dror
D
Drapkin
Ronny
R
Miron
Alexander
A
Mok
Samuel C
SC
Randrianarison
Voahangy
V
Brodie
Steven
S
Salstrom
Jennifer
J
Rasmussen
Theodore P
TP
Klimke
Ann
A
Marrese
Christine
C
Marahrens
York
Y
Deng
Chu Xia
CX
Feunteun
Jean
J
Livingston
David M
DM
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*
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