Molecular Biology

Suppressing Expression of X

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Science  08 Nov 2002:
Vol. 298, Issue 5596, pp. 1137
DOI: 10.1126/science.298.5596.1137d

BRCA1 is a tumor suppressor protein intimately associated with breast and ovarian cancer and has been implicated in a wide range of nuclear functions, including genomic integrity, transcription regulation, chromatin remodeling, and cell cycle checkpoint control. It has been noted previously that in female somatic cells containing a pair of X chromosomes, BRCA1 is associated with the inactive one (Xi). The inactive X chromosome is coated with RNA from the noncoding, Xi-specific transcript (XIST) gene as well as the variant histone MH2A1.

Ganesan et al. show that BRCA1 colocalizes with XIST RNA and that loss of BRCA1 results in loss of XIST from Xi, as well as loss of methylation at lysine 9 of histone H3, both of which are important for the suppression of gene expression. As a result, at least one formerly silenced gene on the inactive X is reactivated. Although BRCA1 and its heterodimeric partner protein BARD1 interact with XIST RNA, these proteins do not affect the level of the RNA; rather, they seem to direct its localization to Xi. — GR

Cell111, 393 (2002).

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