Forming facultative heterochromatin: silencing of an X chromosome in mammalian females

Abstract

Compensating for the dosage difference in X-linked genes between male and female mammals involves the formation of an extremely stable heterochromatin structure on one of the two X chromosomes in females. The inactive X acquires numerous features of silent chromatin, including the expression of a noncoding RNA, a switch to late replication, histone modifications, recruitment of the histone variant macroH2A and DNA hypermethylation. Although the induction of inactivation in differentiating mouse embryonic stem cells suggests that the onset of each of these features appears to occur in a sequential manner, it is likely that there is a much more complex interplay between the different features which leads to the extremely stable silencing observed in female somatic cells. Expression of the untranslated RNA, XIST, is required in cis for the establishment of the heterochromatic state. Recent results have started to elucidate how expression of Xist is controlled, including the role of the antisense transcript Tsix.