DNA Methylation

DNA methylation at the promoters of X-linked genes is important to maintain their transcriptional repression on the Xi. DNA methylation of the Xist promoter, mediated by Dnmtl and Dnmt3a, also contributes to silencing the Xist gene on the Xa (Panning and Jaenisch 1996; Chen et al. 2003). Male cells deficient in Dnmtl exhibit hypomethylation of the Xist promoter region, ectopic expression of Xist RNA, and transcriptional silencing on the single X chromosome (Beard et al. 1995; Panning and Jaenisch 1996). The Xist promoter region is also hypomethylated and Xist is expressed in male mutant cells lacking Dnmt3a and Dnmt3b (Chen et al. 2003; Sado et al. 2004). Adding back Dnmt3a,but not Dnmt3b, to these double mutant cells restored wild-type levels of Xist promoter methylation (Chen et al. 2003). Together these results suggest that multiple methyltransferases prevent Xist expression on the Xa by maintaining methylation patterns at the Xist locus.

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