X chromosome inactivation: silencing, topology and reactivation

- Inactivation of one X chromosome in female cells levels X-linked gene dosage to males.
- The number of known Xist RNA interactor proteins and its functions have widely increased.
- The active and inactive X chromosome have a different topological conformations.
- The reactivation of the inactive X chromosome might be implicated in disease.

To ensure X-linked gene dosage compensation between females (XX) and males (XY), one X chromosome undergoes X chromosome inactivation (XCI) in female cells. This process is tightly regulated throughout development by many different factors, with Xist as a key regulator, encoding a long non-coding RNA, involved in establishment of several layers of repressive epigenetic modifications. Several recent studies on XCI focusing on identification and characterization of Xist RNA-protein interactors, revealed new factors involved in gene silencing, genome topology and nuclear membrane attachment, amongst others. Also, new insights in higher order chromatin organization have been presented, revealing differences between the topological organization of active and inactive X chromosomes (Xa and Xi), with associated differences in gene expression. Finally, further evidence indicates that the inactive state of the Xi can be (partially) reversed, and that this X chromosome reactivation (XCR) might be associated with disease.