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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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Development ePress online publication date 5 Dec 2007
doi: 10.1242/dev.008490
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Crucial role of antisense transcription across the Xist promoter in Tsix-mediated Xist chromatin modification
* Author for correspondence (e-mail: tsado{at}lab.nig.ac.jp)
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J. T. Lee
Lessons from X-chromosome inactivation: long ncRNA as guides and tethers to the epigenome
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X chromosome inactivation in the absence of Dicer
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Y. Hoki, N. Kimura, M. Kanbayashi, Y. Amakawa, T. Ohhata, H. Sasaki, and T. Sado
A proximal conserved repeat in the Xist gene is essential as a genomic element for X-inactivation in mouse
Development,
January 1, 2009;
136(1):
139 - 146.
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T. Ohhata, Y. Hoki, H. Sasaki, and T. Sado
Crucial role of antisense transcription across the Xist promoter in Tsix-mediated Xist chromatin modification
J. Cell Sci.,
January 15, 2008;
121(2):
e1 - e1.
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© The Company of Biologists Ltd 2007