Abstract
In mammals, the dosage imbalance between males and females resulting from the presence of heteromorphie sex chromosomes is compensated for by the inactivation of one X-chromosome in females. This process, which is initiated during the early embryonic development and maintained throughout the life of the individual, is a paradigm for epigenetic regulation, involving as it does the differential treatment of two chromosome homologues within the same nucleus.
So far, X-chromosome inactivation has been mostly studied in the mouse, where it was shown to be controlled by a series of long non-coding RNAs (lncRNAs), at the center of which is Xist. Xist is a nuclear transcript which coats the chromosome from which is it expressed and induces its silencing. Tight control of Xist is critical for ensuring its developmentally regulated, female-specific, mono-allelic expression. The regulation of Xist is mediated by a complex network of trans-acting protein factors and lncRNAs.
Remarkably, genes producing the lncRNAs involved in X-inactivation are all clustered in a single locus of the X-chromosome called the X-inactivation center (Xie). This -1Mb-long locus is overall conserved across eutherian mammals. Xist in particular is found in ali eutherians where it is supposed to play similar role as in the mouse, although this has not been formally demonstrated. In addition, the involvement of additional lncRNAs in controlling XCI in mammalian species other than mouse has not been investigated. We are addressing the role of XIST and other non-coding transcripts in human XCI. We have recently discovered a novel lncRNA, XACT, which coats the active X-chromosome specifically in human early embryonic stages, at the time when XCI is established. The potential role of XIST and XACT in controlling the activity of the X-chromosomes in human will be discussed.
