The XIST noncoding RNA functions independently of BRCA1 in X inactivation.
Females with germline mutations in BRCA1 are predisposed to develop breast and ovarian cancers. A previous report indicated that BRCA1 colocalizes with and is necessary for the correct localization of XIST, a noncoding RNA that coats the inactive X chromosome (Xi) to mediate formation of facultative heterochromatin. A model emerged from this study suggesting that loss of BRCA1 in female cells could reactivate genes on the Xi through loss of the XIST RNA. However, our independent studies of BRCA1 and XIST RNA revealed little evidence to support this model. We report that BRCA1 is not enriched on XIST RNA-coated chromatin of the Xi. Neither mutation nor depletion of BRCA1 causes significant changes in XIST RNA localization or X-linked gene expression. Together, these results do not support a role for BRCA1 in promoting XIST RNA localization to the Xi or regulating XIST-dependent functions in maintaining the stability of facultative heterochromatin.
Xiao
Cuiying
C
Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, 10/9N105, National Institutes of Health, Bethesda, MD 20892, USA.
Sharp
Judith A
JA
Kawahara
Misako
M
Davalos
Albert R
AR
Difilippantonio
Michael J
MJ
Hu
Ying
Y
Li
Wenmei
W
Cao
Liu
L
Buetow
Ken
K
Ried
Thomas
T
Chadwick
Brian P
BP
Deng
Chu-Xia
CX
Panning
Barbara
B
D000818:Animals; D019313:BRCA1 Protein / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D041321:Chromosomes, Human, X; D004622:Embryo, Mammalian / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D019398:Genes, BRCA1; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009154:Mutation; D034622:RNA Interference; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000378:metabolism*; D014960:X Chromosome; D049951:X Chromosome Inactivation
D019313:BRCA1 Protein; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; C077885:XIST non-coding RNA