G9a-mediated irreversible epigenetic inactivation of Oct-3/4 during early embryogenesis
G9a-mediated irreversible epigenetic inactivation of Oct-3/4 during early embryogenesis
复制标题
DOI：
10.1038/ncb1353
复制
发表时间：
2006-02-01
影响因子：
21.3
通讯作者：
Bergman, Y
中科院分区：
文献类型：
--
作者：
Feldman, N;Gerson, A;Bergman, Y
Oct-3/4是一种POU结构域同源异型盒基因，在配子发生期间和早期胚胎细胞中表达（1，2），已显示其对维持多能性很重要（3）。植入后，该基因经历了一个新的多步失活程序。转录抑制之后是由含SET蛋白G9 a介导的组蛋白H3甲基化在Lys 9上的显著增加。这一步骤为通过HP 1结合的局部异染色质化奠定了基础，并且是随后通过酶Dnmt 3a/3b在启动子处进行从头甲基化所必需的。遗传学研究表明，这些表观遗传变化实际上在抑制Oct-3/4再表达中起着重要作用，从而阻止了重编程。
Oct-3/4 is a POU domain homeobox gene that is expressed during gametogenesis and in early embryonic cells(1,2), where it has been shown to be important for maintaining pluripotency(3). Following implantation, this gene undergoes a novel multi-step programme of inactivation. Transcriptional repression is followed by a pronounced increase in histone H3 methylation on Lys 9 that is mediated by the SET-containing protein, G9a. This step sets the stage for local heterochromatinization via the binding of HP1 and is required for subsequent de novo methylation at the promoter by the enzymes Dnmt3a/3b. Genetic studies show that these epigenetic changes actually have an important role in the inhibition of Oct-3/4 reexpression, thereby preventing reprogramming.