X inactivation in the mouse embryo deficient for Dnmt1: distinct effect of hypomethylation on imprinted and random X inactivation.
X inactivation in the mouse embryo deficient for Dnmt1: distinct effect of hypomethylation on imprinted and random X inactivation.
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DOI：
10.1006/dbio.2000.9823
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发表时间：
2000-09
影响因子：
2.7
通讯作者：
T. Sado;M. Fenner;Seong‐Seng Tan;P. Tam;Toshihiro Shioda;En Li
中科院分区：
文献类型：
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作者：
T. Sado;M. Fenner;Seong‐Seng Tan;P. Tam;Toshihiro Shioda;En Li
已有研究表明，DNA甲基化在基因组印迹和X失活中起重要作用。利用携带X连锁LacZ转基因基因的DNA甲基转移酶1(DNMT1)缺陷小鼠胚胎，研究了基因组去甲基化对X失活的影响。根据LacZ的表达模式，在Dnmt1突变胚胎中，内脏内胚层中印记X的失活没有受到影响，而其他印记基因则表现出异常表达。然而，由于低甲基化，Dnmt1突变胚胎的胚胎谱系中的随机X失活是不稳定的，导致至少一个最初被抑制的LacZ转基因基因重新激活。我们的结果表明，在胚外谱系中维持印记X失活可以耐受广泛的去甲基化，而在胚胎谱系中维持稳定的X失活需要正常水平的甲基化。
It has been suggested that DNA methylation plays a crucial role in genomic imprinting and X inactivation. Using DNA methyltransferase 1 (Dnmt1)-deficient mouse embryos carrying X-linked lacZ transgenes, we studied the effects of genomic demethylation on X inactivation. Based on the expression pattern of lacZ, the imprinted X inactivation in the visceral endoderm, a derivative of the extraembryonic lineage, was unaffected in Dnmt1 mutant embryos at the time other imprinted genes showed aberrant expression. Random X inactivation in the embryonic lineage of Dnmt1 mutant embryos, however, was unstable as a result of hypomethylation, causing reactivation of, at least, one lacZ transgene that had initially been repressed. Our results suggest that maintenance of imprinted X inactivation in the extraembryonic lineage can tolerate extensive demethylation while normal levels of methylation are required for stable maintenance of X inactivation in the embryonic lineage.