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Publication : Crucial role of antisense transcription across the Xist promoter in Tsix-mediated Xist chromatin modification.

First Author  Ohhata T Year  2008
Journal  Development Volume  135
Issue  2 Pages  227-35
PubMed ID  18057104 Mgi Jnum  J:130425
Mgi Id  MGI:3771664 Doi  10.1242/dev.008490
Citation  Ohhata T, et al. (2008) Crucial role of antisense transcription across the Xist promoter in Tsix-mediated Xist chromatin modification. Development 135(2):227-35
abstractText  Expression of Xist, which triggers X inactivation, is negatively regulated in cis by an antisense gene, Tsix, transcribed along the entire Xist gene. We recently demonstrated that Tsix silences Xist through modification of the chromatin structure in the Xist promoter region. This finding prompted us to investigate the role of antisense transcription across the Xist promoter in Tsix-mediated silencing. Here, we prematurely terminated Tsix transcription before the Xist promoter and addressed its effect on Xist silencing in mouse embryos. We found that although 93% of the region encoding Tsix was transcribed, truncation of Tsix abolished the antisense regulation of Xist. This resulted in a failure to establish the repressive chromatin configuration at the Xist promoter on the mutated X, including DNA methylation and repressive histone modifications, especially in extraembryonic tissues. These results suggest a crucial role for antisense transcription across the Xist promoter in Xist silencing.
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