What makes the maternal X chromosome resistant to undergoing imprinted X inactivation?

In the mouse, while either X chromosome is chosen for inactivation in a random fashion in the embryonic tissue, the paternally derived X chromosome is preferentially inactivated in the extraembryonic tissues. It has been shown that the maternal X chromosome is imprinted so as not to undergo inactivation in the extraembryonic tissues. X-linked noncodingXist RNA becomes upregulated on the X chromosome that is to be inactivated. An antisense noncoding RNA,Tsix , which occurs at theXist locus and has been shown to negatively regulateXist expression in cis, is imprinted to be expressed from the maternal X in the extraembryonic tissues. AlthoughTsix appears to be responsible for the imprint laid on the maternal X, those who disagree with this idea would point out the fact thatTsix has not yet been expressed from the maternal X whenXist becomes upregulated on the paternal but not the maternal X at the onset of imprinted X-inactivation in preimplantation embryos. Recent studies have demonstrated, however, that there is a prominent difference in the chromatin structure at theXist locus depending on the parental origin, which I suggest might account for the repression of maternalXist in the absence of maternalTsix at the preimplantation stages.This article is part of the themed issue ‘X-chromosome inactivation: a tribute to Mary Lyon’.