Xist at the edge: silencing at the nuclear periphery extends to X inactivation

The physical organization of chromatin in the nucleus plays a fundamental role in directing developmental cell fate decisions. The nuclear lamina in particular is a critical regulator of silencing specific genomic regions and establishing facultative heterochromatin (1). Chen et al. now demonstrate the connection between Xist-mediated silencing of the inactive X chromosome (XCI) and the repressive properties of the nuclear lamina (2). The absence of the inactive X chromosome has long been associated with tumors (3), and lately Xist, along with other long noncoding RNAs (lncRNAs), has been implicated in cancer etiology in addition to its role in dosage compensation (4,5). These new findings emphasize the links between the Xist lncRNA, repressive epigenetic modifiers such as the polycomb repressive complexes (PRC1, PRC2), histone deacetylase 3 (HDAC3)-containing complexes, and the nuclear lamina, pointing towards new directions in the role of epigenetic silencing in translational cancer research.