Department of Internal Medicine, Division of Molecular Medicine and Genetics, University of Michigan Medical School, 1150 W. Medical Center Drive, 5560 MSRBII, Ann Arbor, MI 48109, USA.
Nucleic Acids Res. 2014 Mar;42(5):2893-905. doi: 10.1093/nar/gkt1261. Epub 2013 Dec 9.
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.
十号十一号易位（TET）家族酶将 5-甲基胞嘧啶转化为 5-羟甲基胞嘧啶。然而，调节这一生物过程的分子机制尚不清楚。在这里，我们证明了 PGC7（也称为 Dppa3 或 Stella）在体外和体内与 TET2 和 TET3 相互作用，以抑制 TET2 和 TET3 的酶活性。此外，缺乏 PGC7 会导致印迹基因座的 DNA 甲基化丢失。PGC7 的全基因组分析揭示了一个被 PGC7 识别的一致 DNA 基序。PGC7 结合基序周围的 CpG 岛呈超甲基化状态。综上所述，我们的研究证明了 PGC7 防止 DNA 甲基化被 TET 家族酶依赖性氧化的分子机制。
