Jin Seung-Gi, Guo Cai, Pfeifer Gerd P
Division of Biology, Beckman Research Institute of the City of Hope, Duarte, California, United States of America.
PLoS Genet. 2008 Mar 7;4(3):e1000013. doi: 10.1371/journal.pgen.1000013.
Although DNA methylation patterns in somatic cells are thought to be relatively stable, they undergo dramatic changes during embryonic development, gametogenesis, and during malignant transformation. The enzymology of DNA methyltransferases is well understood, but the mechanism that removes methylated cytosines from DNA (active DNA demethylation) has remained enigmatic. Recently, a role of the growth arrest and DNA damage inducible protein GADD45A in DNA demethylation has been reported [1]. We have investigated the function of GADD45A in DNA demethylation in more detail using gene reactivation and DNA methylation assays. Contrary to the previous report, we were unable to substantiate a functional role of GADD45A in DNA demethylation. The mechanism of active DNA demethylation in mammalian cells remains unknown.
虽然体细胞中的DNA甲基化模式被认为相对稳定，但它们在胚胎发育、配子发生以及恶性转化过程中会发生显著变化。DNA甲基转移酶的酶学机制已得到充分了解，但从DNA中去除甲基化胞嘧啶的机制（活性DNA去甲基化）仍然是个谜。最近，有报道称生长停滞和DNA损伤诱导蛋白GADD45A在DNA去甲基化中发挥作用[1]。我们使用基因重新激活和DNA甲基化分析更详细地研究了GADD45A在DNA去甲基化中的功能。与之前的报道相反，我们无法证实GADD45A在DNA去甲基化中具有功能作用。哺乳动物细胞中活性DNA去甲基化的机制仍然未知。
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