PGC7 suppresses TET3 for protecting DNA methylation.

PGC7 suppresses TET3 for protecting DNA methylation.
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DOI:
10.1093/nar/gkt1261
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发表时间:
2014-03
影响因子:
14.9
通讯作者:
Yu X
Yu X
中科院分区:
生物学2区
文献类型:
--
作者:
Bian C;Yu X

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10-11易位(Tet)家族酶将5-甲基胞嘧啶转化为5-羟甲基胞嘧啶。然而,调控这一生物过程的分子机制尚不清楚。在这里,我们展示了PGC7(也称为Dppa3或Stella)在体外和体内都与TET2和TET3相互作用的证据,以抑制TET2和TET3的酶活性。此外,缺少PGC7会导致印迹基因座上DNA甲基化的丢失。对PGC7的全基因组分析显示了一个被PGC7识别的一致的DNA基序。PGC7结合基序周围的CpG岛被超甲基化。综上所述,我们的研究证明了PGC7保护DNA甲基化免受Tet家族酶依赖性氧化的分子机制。
Ten-eleven translocation (TET) family enzymes convert 5-methylcytosine to 5-hydroxylmethylcytosine. However, the molecular mechanism that regulates this biological process is not clear. Here, we show the evidence that PGC7 (also known as Dppa3 or Stella) interacts with TET2 and TET3 both in vitro and in vivo to suppress the enzymatic activity of TET2 and TET3. Moreover, lacking PGC7 induces the loss of DNA methylation at imprinting loci. Genome-wide analysis of PGC7 reveals a consensus DNA motif that is recognized by PGC7. The CpG islands surrounding the PGC7-binding motifs are hypermethylated. Taken together, our study demonstrates a molecular mechanism by which PGC7 protects DNA methylation from TET family enzyme-dependent oxidation.
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发表时间: 2011-08-29
期刊: Genome biology
影响因子: 12.3
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