The Coupling of X-Chromosome Inactivation to Pluripotency

X-chromosome inactivation, or the silencing of one X chromosome that occurs initially in the female somatic four-cell-stage embryo, is reversed during embryonic development first at the time of inner cell mass formation and again during formation of germ cell precursors. Such X-chromosome reactivation in the mouse implies the silencing of the Xist gene and the transcription of its antisense partner, Tsix, from both X chromosomes. In murine embryonic stem cells, both genes are under the transcriptional control of a series of critical pluripotency factors, namely, OCT3/4, NANOG, SOX2, KLF4, C-MYC and REX1. Although the inactive/active status of the two X chromosomes present in female human embryonic stem cells remains controversial, the reactivation of X-chromosome inactivation seems to be a signature for the naive pluripotent state.