Fig. 1. Model depicting chromatin events during X-chromosome inactivation (XCI). (A) Before XCI, Tsix (red) is biallelically expressed and maintains the Tsix/Xist locus in an open chromatin state (bearing the active H4 acetyl and H3H4 dimethyl histone marks), which paradoxically precludes Xist transcription (blue). (B) At the onset of XCI, silencing of Tsix induces local heterochromatinization of the Tsix/Xist locus in cis (loss of H4 acetyl and H3H4 dimethyl, gain of H3H27 trimethyl), concomitant with activation of Xist in the future inactive X (Xi). (C) On the future active X (Xa), Tsix RNA induces Dnmt3a-dependent methylation of Xist, locking it into a silent state. (D) Finally, the Xist locus switches to a canonical chromatin state, with active marks on the transcribing allele (bottom) and inactive marks on the silent one (top). Reproduced, with permission, from Sun et al. (Sun et al., 2006).