Navarro Pablo, Page Damian R, Avner Philip, Rougeulle Claire
Unité de Génétique Moléculaire Murine, Institut Pasteur 75724, Paris Cedex 15, France.
Genes Dev. 2006 Oct 15;20(20):2787-92. doi: 10.1101/gad.389006.
Initiation of X inactivation depends on the coordinated expression of the sense/antisense pair Xist/Tsix. We show here that a precisely defined Xist promoter region flanked by CTCF is maintained by Tsix in a heterochromatic-like state in undifferentiated embryonic stem (ES) cells and shifts to a pseudoeuchromatic structure upon Tsix truncation. We further demonstrate that the epigenetic state of the Xist 5' region prior to differentiation predicts the efficiency of transcriptional machinery recruitment to the Xist promoter during differentiation. Our results provide mechanistic insights into the Tsix-mediated epigenetic regulation of Xist resulting in Xist promoter activation and initiation of X inactivation in differentiating ES cells.
X染色体失活的起始依赖于Xist/Tsix正义/反义基因对的协同表达。我们在此表明，由CTCF侧翼包围的一个精确定义的Xist启动子区域，在未分化的胚胎干细胞中由Tsix维持在类似异染色质的状态，并在Tsix截短后转变为假常染色质结构。我们进一步证明，分化前Xist 5'区域的表观遗传状态可预测分化过程中转录机制募集到Xist启动子的效率。我们的结果为Tsix介导的Xist表观遗传调控提供了机制性见解，该调控导致分化中的胚胎干细胞中Xist启动子激活和X染色体失活的起始。
