LOSS OF METHYLATION ACTIVATES XIST IN SOMATIC BUT NOT IN EMBRYONIC-CELLS
LOSS OF METHYLATION ACTIVATES XIST IN SOMATIC BUT NOT IN EMBRYONIC-CELLS
复制标题
DOI：
10.1101/gad.9.19.2325
复制
发表时间：
1995-10-01
影响因子：
10.5
通讯作者：
JAENISCH, R
中科院分区：
文献类型：
--
作者：
BEARD, C;LI, E;JAENISCH, R
小鼠Xist基因仅在失活的X染色体上表达，被认为在X染色体失活的起始过程中发挥作用。该基因的5'端在活性X染色体上完全甲基化，而在失活的X染色体上则完全去甲基化，这表明DNA甲基化可能参与控制该基因的等位基因特异性转录。为了直接研究DNA甲基化在控制Xist表达中的重要性，我们检测了其在缺乏DNA甲基转移酶活性的胚胎干细胞（ES细胞）和胚胎中的甲基化模式及表达情况。我们在此报道，雄性突变胚胎中Xist基因座的去甲基化诱导了Xist表达，从而在原肠胚形成后的胚胎中建立了去甲基化与Xist基因表达之间的直接联系。然而，未分化的ES细胞中Xist的转录活性似乎与其甲基化状态无关。这些结果表明，甲基化可能只有在ES细胞分化后或胚胎经过原肠胚形成后才对Xist的抑制至关重要。
The mouse Xist gene, which is expressed only from the inactive X chromosome, is thought to play a role in the initiation of X inactivation. The 5' end of this gene is fully methylated on the active X chromosome and completely demethylated on the inactive X chromosome, suggesting that DNA methylation may be involved in controlling allele-specific transcription of this gene. To directly investigate the importance of DNA methylation in the control of Xist expression, we have examined its methylation patterns and expression in ES cells and embryos that are deficient in DNA methyltransferase activity. We report here that demethylation of the Xist locus in male mutant embryos induces Xist expression, thus establishing a direct link between demethylation and expression of the Xist gene in the postgastrulation embryo. The transcriptional activity of Xist in undifferentiated ES cells, however, appears to be independent of its methylation status. These results suggest that methylation may only become essential for Xist repression after ES cells have differentiated or after the embryo has undergone gastrulation.