Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Room 3128, Building 37, Bethesda, MD 20892, United States.
Department of Biochemistry, North Carolina State University, 128 Polk Hall, Raleigh, NC 27695, United States.
Biochem Biophys Res Commun. 2014 Jun 27;449(2):248-55. doi: 10.1016/j.bbrc.2014.05.018. Epub 2014 May 14.
Three oxidative products of 5-methylcytosine (5mC) occur in mammalian genomes. We evaluated if these cytosine modifications in a CG dinucleotide altered DNA binding of four B-HLH homodimers and three heterodimers to the E-Box motif CGCAG|GTG. We examined 25 DNA probes containing all combinations of cytosine in a CG dinucleotide and none changed binding except for carboxylation of cytosine (5caC) in the strand CGCAG|GTG. 5caC enhanced binding of all examined B-HLH homodimers and heterodimers, particularly the Tcf3|Ascl1 heterodimer which increased binding ~10-fold. These results highlight a potential function of the oxidative products of 5mC, changing the DNA binding of sequence-specific transcription factors.
哺乳动物基因组中存在 5-甲基胞嘧啶（5mC）的三种氧化产物。我们评估了 CG 二核苷酸中这些胞嘧啶修饰是否改变了四个 B-HLH 同源二聚体和三个异源二聚体与 E-Box 基序 CGCAG|GTG 的 DNA 结合。我们研究了 25 个包含 CG 二核苷酸中所有胞嘧啶组合的 DNA 探针，除了 CGCAG|GTG 链上的胞嘧啶羧化（5caC）外，没有任何改变结合的情况。5caC 增强了所有被检查的 B-HLH 同源二聚体和异源二聚体的结合，特别是 Tcf3|Ascl1 异源二聚体的结合增加了约 10 倍。这些结果突出了 5mC 的氧化产物的潜在功能，改变了序列特异性转录因子的 DNA 结合。
