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. 2009 Aug 15;23(16):1831–1842. doi: 10.1101/gad.1811209

Figure 5.

Figure 5.

Tsix RNA as molecular switch for Xa and Xi. Adapted from Sun et al. (2006) with permission from Elsevier. Before XCI, biallelic expression of Tsix RNA enables the Tsix/Xist alleles on both Xs to remain euchromatic, as indicated by biallelic H3-K4 dimethylation and H4 acetylation. Paradoxically, the euchromatic state precludes Xist transcription. At the onset of XCI, silencing of Tsix on one X (future Xi) results in pre-emptive heterochromatin formation across the 40-kb Tsix/Xist locus, as indicated by loss of H3-K4me2 and H4 acetylation, and gain of H3-K27me3. Xist is poised and transactivated 100-fold upon cell differentiation. On the future Xa, persistent Tsix RNA expression maintains the 40-kb Tsix/Xist locus in cis in a euchromatic configuration. During the establishment phase, Tsix RNA also recruits the activity of Dnmt3a to the Xist promoter to methylate (lollipops) and lock in the silent state of Xist. Dnmt3a methylation is hypothetically mediated by small RNAs created from long Xist:Tsix dsRNA via the RNAi pathway in a manner similar to RDDM and TGS in yeast and plants. This idea remains to be tested.