The Polycomb group (PcG) protein Eed is implicated in regulation of imprinted X-chromosome inactivation in extraembryonic cells but not of random X inactivation in embryonic cells. The Drosophila homolog of the Eed-Ezh2 PcG protein complex achieves gene silencing through methylation of histone H3 on lysine 27 (H3-K27), which suggests a role for H3-K27 methylation in imprinted X inactivation. Here we demonstrate that transient recruitment of the Eed-Ezh2 complex to the inactive X chromosome (Xi) occurs during initiation of X inactivation in both extraembryonic and embryonic cells and is accompanied by H3-K27 methylation. Recruitment of the complex and methylation on the Xi depend on Xist RNA but are independent of its silencing function. Together, our results suggest a role for Eed-Ezh2–mediated H3-K27 methylation during initiation of both imprinted and random X inactivation and demonstrate that H3-K27 methylation is not sufficient for silencing of the Xi.

Understanding Xist-ance: Large noncoding RNAs (lncRNAs) are increasingly appreciated to play important roles in the cell. A number of lncRNAs act to target chromatin regulatory complexes to their sites of action. Engreitz et al. (p. 10.1126/science.1237973 , published online 4 July; see the Perspective by Dimond and Fraser ) found that the mouse Xist lncRNA, which initiates X-chromosome inactivation, was transferred from its site of transcription to distant sites on the X chromosome purely through their close three-dimensional proximity to the Xist gene. Xist initially localized to the periphery of active genes on the X chromosome but gradually spread across them using its A-repeat domain, until the Xist RNA bound broadly across the inactive X chromosome in differentiated female cells.