X chromosome inactivation in stem cells and development

In mammals, gene dosage of X-chromosomal genes is equalized between the sexes by random inactivation of either one of the two X chromosomes in female cells. Xchromosome inactivation (XCI) is initiated early during female embryonic development and can be recapitulated upon differentiation of female embryonic stem cells (ES). In this chapter, we provide a comprehensive review of XCI regulation in mammals, but also briefly highlight different dosage compensation strategies that evolved in other organisms. Important cis and trans acting regulators of XCI are presented, as well as factors involved in the maintenance of XCI. We also discuss different models that have been postulated to explain initiation of XCI in female cells. Finally, we describe X chromosome reactivation (XCR) in mouse development and the potential of induced pluripotent stem cells (iPSCs) as a model system to study the XCI process in mouse and human.