De novo DNA methylation promoted by G9a prevents reprogramming of embryonically silenced genes.
De novo DNA methylation promoted by G9a prevents reprogramming of embryonically silenced genes.
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DOI：
10.1038/nsmb.1476
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发表时间：
2008-11
影响因子：
16.8
通讯作者：
Bergman, Yehudit
中科院分区：
文献类型：
--
作者：
Epsztejn-Litman, Silvina;Feldman, Nirit;Abu-Remaileh, Monther;Shufaro, Yoel;Gerson, Ariela;Ueda, Jun;Deplus, Rachel;Fuks, Francois;Shinkai, Yoichi;Cedar, Howard;Bergman, Yehudit
多能性决定基因Oct-3/4（也称为Pou5f1）在由组蛋白甲基转移酶（HMT） G9a介导的过程中经历着床后沉默。微阵列分析显示，该酶可能作为一种主调控因子，通过甲基化组蛋白H3K9异染色质化和从头DNA甲基化使多个早期胚胎基因失活。分化ES细胞的遗传学研究表明，G9a SET结构域的点突变阻止异染色质化，但仍允许从头甲基化，而生化和功能研究表明，G9a本身能够通过其锚蛋白（ANK）结构域，通过招募Dnmt3a/3b而独立于其HMT活性，从而实现从头甲基化。这些修饰似乎是为了执行两种独立的生物学功能而编程的，组蛋白甲基化在缺乏转录抑制因子的情况下阻断靶基因的再激活，而DNA甲基化则阻止重编程到未分化状态。
The pluripotency determining gene, Oct-3/4 (also called Pou5f1) undergoes post implantation silencing in a process mediated by the histone methyltransferase (HMT) G9a. Microarray analysis now shows that this enzyme may operate as a master regulator that inactivates multiple early embryonic genes by bringing about methylated-histone H3K9 heterochromatinization and de novo DNA methylation. Genetic studies in differentiating ES cells demonstrate that a point mutation in the G9a SET domain prevents heterochromatinization, but still allows de novo methylation, while biochemical and functional studies indicate that G9a itself is capable of bringing about de novo methylation through its ankyrin (ANK) domain, by recruiting Dnmt3a/3b independently of its HMT activity. These modifications appear to be programmed for carrying out two separate biological functions, with histone methylation blocking target-gene reactivation in the absence of transcriptional repressors, while DNA methylation prevents reprogramming to the undifferentiated state.
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影响因子：
64.5
作者：
Mitsui, K;Tokuzawa, Y;Yamanaka, S
通讯作者：
Yamanaka, S
影响因子：
14.9
作者：
Deplus, R;Brenner, C;Fuks, F
通讯作者：
Fuks, F
影响因子：
16
作者：
Freitag, M;Hickey, PC;Selker, EU
通讯作者：
Selker, EU
影响因子：
10.5
作者：
Esteve, Pierre-Olivier;Chin, Hang Gyeong;Pradhan, Sriharsa
通讯作者：
Pradhan, Sriharsa
影响因子：
9.2
作者：
Lehnertz, B;Ueda, Y;Peters, AHFM
通讯作者：
Peters, AHFM