In female mammals, the non-coding Xist RNA triggers the inactivation of one X chromosome early in embryogenesis to compensate for X chromosome gene dosage. But what maintains X inactivation in differentiated cells? On p. 935, Anton Wutz and colleagues identify the Trithorax group protein Ash2l as a novel factor that, together with the histone variant macroH2A and the nuclear scaffold protein Saf-A, maintains the inactive X chromosome (Xi) in differentiated mouse cells. The researchers show that these three factors are recruited concomitantly by Xist at the transition to Xi maintenance in differentiating mouse embryonic stem cells. Interestingly, expression of a mutant Xist that does not initiate gene silencing nevertheless triggers the recruitment of these factors to Xi. Other results suggest that expression of Xist early in ES cell differentiation induces a ‘chromosomal memory’ that later recruits Ash21, Saf-A and macroH2A to Xi to maintain gene silencing, thus revealing that the spatial organisation of chromatin changes plays a crucial role in the maintenance of X inactivation.