Differential regulation of genomic imprinting by TET proteins in embryonic stem cells.
Differential regulation of genomic imprinting by TET proteins in embryonic stem cells.
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DOI：
10.1016/j.scr.2015.08.010
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发表时间：
2015-09
影响因子：
1.2
通讯作者：
Li X
中科院分区：
文献类型：
--
作者：
Liu L;Mao SQ;Ray C;Zhang Y;Bell FT;Ng SF;Xu GL;Li X
已发现Tet蛋白在哺乳动物CpG位点的主动去甲基化中起重要作用。有一些报道表明，它们在去除生殖系印迹区域的DNA甲基化印记方面具有一定的功能。然而，Tet蛋白是否也参与了胚胎干细胞DNA甲基化印迹的去甲基化还没有得到很好的证实。在这里，我们报告了Tet蛋白的丢失导致ES细胞中Igf2-H19印迹区域DNA甲基化的显著增加。我们还观察到在没有Tet蛋白的ES克隆中，特别是在分化的ES细胞中，Peg1印迹区域的DNA甲基化水平有不同程度的增加。相反，我们没有观察到缺乏Tet蛋白的ES细胞在Peg3、Snrpn和Dlk1-dio3印迹区域的DNA甲基化印迹显著增加。有趣的是，Tet蛋白的缺失并没有导致类胚体(EB)中Igf2-H19和Peg1印迹区域DNA甲基化印迹的显著增加。因此，Tet蛋白似乎不同地参与维持ES细胞和EBS中印迹区域的DNA甲基化印迹。
TET proteins have been found to play an important role in active demethylation at CpG sites in mammals. There are some reports implicating their functions in removal of DNA methylation imprint at the imprinted regions in the germline. However, it is not well established whether TET proteins can also be involved in demethylation of DNA methylation imprint in embryonic stem (ES) cells. Here we report that loss of TET proteins caused significant increase in DNA methylation at the Igf2-H19 imprinted region in ES cells. We also observed variable increase in DNA methylation at the Peg1 imprinted region in the ES clones devoid of TET proteins, in particular in the differentiated ES cells. By contrast, we did not observe significant increase of DNA methylation imprint at the Peg3, Snrpn and Dlk1-Dio3 imprinted regions in ES cells lacking TET proteins. Interestingly, loss of TET proteins did not result in significant increase of DNA methylation imprint at the Igf2-H19 and Peg1 imprinted regions in the embryoid bodies (EB). Therefore, TET proteins seem to be differentially involved in maintaining DNA methylation imprint at a subset of imprinted regions in ES cells and EBs.