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

Tatsuya Ohhata, Yuko Hoki, Hiroyuki Sasaki, Takashi Sado

Research output: Contribution to journalArticlepeer-review

100 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)227-235
Number of pages9
JournalDevelopment
Volume135
Issue number2
DOIs
Publication statusPublished - Jan 1 2008
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Developmental Biology

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