fig1

Figure 1. Model of X chromosome inactivation (XCI) in female embryos. (A, B) Imprinted and random XCI during development. XCI occurs in two distinct Xist-dependent waves. (A) The first phase is the imprinted XCI that commences at the two-to-four cell stages. Cells in the female embryo initiate the imprinted XCI that selectively inactivates the Xist coated paternal X chromosome (Xp). Xist expression from the maternal X chromosome (Xm) is inhibited due to the imprint signatures. RNF12 is a trans-activator that functions in the imprinted XCI in a dose-dependent manner. (B) As the embryo further develops into a blastocyst, Xp is reactivated in the pre-epiblast cells of inner cell mass (ICM). Subsequent initiation of random XCI (rXCI) occurs in ICM right after implantation and randomly affects either the Xp or Xm. Inactive state is stably maintained through further mitosis in the soma cells. Two copies of Rnf12 were also suggested to be necessary to activate Xist during random XCI. (C) Model of the sequence of events leading to silencing of X chromosome. Random XCI has three well-demarcated stages: initiation, establishment, and maintenance. Upon initiation Xist is regulated by several cis and trans-regulatory factors. Xist up-regulation in cis is followed by its tethering to the nucleation center by YY1, silencing then further spreads on the entire X chromosome. Xist recruits Polycomb repressive complexes (PRC 1 and 2), histone deacetylase 3 (HDAC3), and DNA (cytosine-5)-methyltransferase 1 (DNMT1), which mediate methylation of H3K27, histone deacethylation and CpG islands methylation respectively