The mechanisms by which Xist RNA associates with the X chromosome to mediate alterations in chromatin structure remain mysterious. Recent genome-wide Xist RNA distribution studies suggest that this long noncoding RNA uses 3-dimensional chromosome contacts to move to its sites of action.
In organisms with XY sex chromosomes, chromatin modifications are directed to the X chromosomes (X) to equalize X-linked gene dosage between males and females. In flies and worms, the dosage compensation complexes are localized to the X by sequence specific binding to high affinity sites and subsequent spread to nearby lower affinity sites. Despite over five decades of X chromosome inactivation (XCI) research, little is understood of the mechanisms controlling the localization of the mammalian dosage compensation machinery to the X. In XCI, a long noncoding RNA (lcnRNA), Xist RNA, recruits chromatin modifying complexes to the X. The Xist gene is encoded in the X-inactivation center (Xic), an X-linked cis-element that is essential for XCI. Xist RNA spreads from the Xic to coat the X and contributes to the initial establishment of silencing and subsequent maintenance of XCI. In two recent studies, Engreitz et al. and Simon et al. used genome-wide approaches to map the DNA associated with Xist RNA to provide insight into how this lncRNA spreads.
- Leung KN, Panning B. (2014) X-inactivation: xist RNA uses chromosome contacts to coat the x. Curr Biol 24(2), R80-2. [abstract]