A functional role for Tsix transcription in blocking Xist RNA accumulation but not in X-chromosome choice

被引:147
作者
Stavropoulos, N
Lu, NF
Lee, JT [1 ]
机构
[1] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA
[2] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA
关键词
D O I
10.1073/pnas.171243598
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
In female mammals, up-regulation of Xist triggers X-chromosome inactivation in cis. Up-regulation is inhibited by sequences 3 ' to Xist contained within the antisense locus, Tsix. inhibition could depend on transcription of Tsix and/or on DNA elements therein. Here we test the role of Tsix transcription by augmenting the duration and strength of Tsix expression. We find that Tsix hypertranscription is sufficient to block Xist RNA accumulation in a cis-limited manner. We propose that Tsix transcription is necessary to restrict Xist activity on the future active X and, conversely, that Tsix repression is required for Xist RNA accumulation on the future inactive X. We also find that Tsix hypertranscription does not affect X-chromosome choice. Thus, choice is mediated by elements within Tsix that are independent of promoter activity.
引用
收藏
页码:10232 / 10237
页数:6
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