Xist RNA and the mechanism of X chromosome inactivation.
Dosage compensation in mammals is achieved by the transcriptional inactivation of one X chromosome in female cells. From the time X chromosome inactivation was initially described, it was clear that several mechanisms must be precisely integrated to achieve correct regulation of this complex process. X-inactivation appears to be triggered upon differentiation, suggesting its regulation by developmental cues. Whereas any number of X chromosomes greater than one is silenced, only one X chromosome remains active. Silencing on the inactive X chromosome coincides with the acquisition of a multitude of chromatin modifications, resulting in the formation of extraordinarily stable facultative heterochromatin that is faithfully propagated through subsequent cell divisions. The integration of all these processes requires a region of the X chromosome known as the X-inactivation center, which contains the Xist gene and its cis-regulatory elements. Xist encodes an RNA molecule that plays critical roles in the choice of which X chromosome remains active, and in the initial spread and establishment of silencing on the inactive X chromosome. We are now on the threshold of discovering the factors that regulate and interact with Xist to control X-inactivation, and closer to an understanding of the molecular mechanisms that underlie this complex process.
Plath
Kathrin
K
Department of Biochemistry & Biophysics, University of California San Francisco, San Francisco, California 94143, USA. kathrin@itsa.ucsf.edu
Mlynarczyk-Evans
Susanna
S
Nusinow
Dmitri A
DA
Panning
Barbara
B
D000818:Animals; D001483:Base Sequence; D002843:Chromatin / Q000235:genetics; D004303:Dosage Compensation, Genetic; D020868:Gene Silencing; D051379:Mice; D012313:RNA / Q000235:genetics*; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000235:genetics*
D002843:Chromatin; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; C077885:XIST non-coding RNA; D012313:RNA