Xist RNA and the mechanism of X chromosome inactivation

• Published in: Annual review of genetics Vol. 36; no. 1; pp. 233 - 278
• Main Authors: Plath, Kathrin, Mlynarczyk-Evans, Susanna, Nusinow, Dmitri A, Panning, Barbara
• Format: Journal Article
• Language: English
• Published: United States Annual Reviews, Inc 01.01.2002
• Subjects: Animals; Base Sequence; Chromatin - genetics; Chromosomes; Dosage Compensation, Genetic; Gene expression; Gene Silencing; Genetics; Inactivation; Mice; Ribonucleic acid; RNA; RNA - genetics; RNA, Long Noncoding; RNA, Untranslated - genetics; X chromosome; United States
• ISSN: 0066-4197; 1545-2948
• DOI: 10.1146/annurev.genet.36.042902.092433

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.