Developmental regulation of X-chromosome inactivation.
With the emergence of sex-determination by sex chromosomes, which differ in composition and number between males and females, appeared the need to equalize X-chromosomal gene dosage between the sexes. Mammals have devised the strategy of X-chromosome inactivation (XCI), in which one of the two X-chromosomes is rendered transcriptionally silent in females. In the mouse, the best-studied model organism with respect to XCI, this inactivation process occurs in different forms, imprinted and random, interspersed by periods of X-chromosome reactivation (XCR), which is needed to switch between the different modes of XCI. In this review, I describe the recent advances with respect to the developmental control of XCI and XCR and in particular their link to differentiation and pluripotency. Furthermore, I review the mechanisms, which influence the timing and choice, with which one of the two X-chromosomes is chosen for inactivation during random XCI. This has an impact on how females are mosaics with regard to which X-chromosome is active in different cells, which has implications on the severity of diseases caused by X-linked mutations.
Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology and Universitat Pompeu Fabra (UPF), Dr. Aiguader, 88, Barcelona 08003, Spain. Electronic address: Bernhard.payer@crg.eu.
Bernhard
B
Payer
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D018392:Genomic Imprinting; D006801:Humans; D009030:Mosaicism; D049951:X Chromosome Inactivation / Q000235:genetics*
Development; Epigenetics; Noncoding RNA; Pluripotency; Reprogramming; X-chromosome inactivation