Transcription factors of pluripotency in the regulation of X chromosome
inactivation. (A) Scheme of the mouse X chromosome inactivation center
(XIC). Xist , Tsix , and their activators
– Rnf12 and Xite – are shown
in red, green, and black, respectively. In undifferentiated female mouse
ESCs, the transcription factors Oct4, Sox2, and Nanog bind to the first
intron of Xist and Rnf12 , repressing
their transcription. Meanwhile, OCt4, Sox2, Klf4, Rex1, and с-Myc bind
to the regulatory regions of Tsix and Xite
, activating their transcription. (B) In female mouse ESCs,
Tsix is activated and Xist is
repressed by the proteins involved in pluripotency maintenance. During the
differentiation, one of the X chromosomes is inactivated. X-inactivation is
a multistage process including the initiation of inactivation,
establishment, and maintenance of transcriptional silencing. Initiation of
inactivation occurs due to the decrease in pluripotency factor expression
and involvement of chromatin structure regulators (such as SATB1 and PRC2)
in the process. Overexpression of Oct4, Sox2, Nanog, and с-Myc in
somatic cells induces reprogramming to the pluripotent state, which is
accompanied by reactivation of the inactive X chromosome [166]