Novel players in X inactivation: insights into Xist-mediated gene silencing and chromosome conformation

The nuclear long noncoding RNA (lncRNA) Xist ensures X-chromosome inactivation (XCI) in female placental mammals. Although Xist is one of the most intensively studied lncRNAs, the mechanisms associated with its capacity to trigger chromosome-wide gene silencing, the formation of facultative heterochromatin and an unusual 3D conformation of the inactive X chromosome (Xi) have remained elusive. Now researchers have identified novel functional partners of Xist in a series of breakthrough studies, using unbiased techniques to isolate Xist-bound proteins, as well as forward genetic screens. In addition, important insights into the 3D organization of Xi and its relation to gene expression have been obtained. In this Review, we discuss how this new information is providing a recipe for deciphering XCI mechanisms by which a multitasking RNA can structurally and functionally transform an active chromosome into uniquely organized facultative heterochromatin.