TY - JOUR
T1 - Crucial role of antisense transcription across the Xist promoter in Tsix-mediated Xist chromatin modification
AU - Ohhata, Tatsuya
AU - Hoki, Yuko
AU - Sasaki, Hiroyuki
AU - Sado, Takashi
PY - 2008/1/1
Y1 - 2008/1/1
N2 - 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.
AB - 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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U2 - 10.1242/dev.008490
DO - 10.1242/dev.008490
M3 - Article
C2 - 18057104
AN - SCOPUS:38949194937
VL - 135
SP - 227
EP - 235
JO - Journal of Embryology and Experimental Morphology
JF - Journal of Embryology and Experimental Morphology
SN - 0950-1991
IS - 2
ER -