Carboxylation of cytosine (5caC) in the CG dinucleotide in the E-box motif (CGCAG|GTG) increases binding of the Tcf3|Ascl1 helix-loop-helix heterodimer 10-fold
Carboxylation of cytosine (5caC) in the CG dinucleotide in the E-box motif (CGCAG|GTG) increases binding of the Tcf3|Ascl1 helix-loop-helix heterodimer 10-fold
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DOI：
10.1016/j.bbrc.2014.05.018
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发表时间：
2014-06-27
影响因子：
3.1
通讯作者：
Vinson, Charles
中科院分区：
文献类型：
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作者：
Golla, Jaya Prakash;Zhao, Jianfei;Vinson, Charles
哺乳动物基因组中存在3种5-甲基胞嘧啶(5mC)的氧化产物。我们评估了CG二核苷酸中的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垂直条GTG的DNA结合。我们检查了25个包含CG二核苷酸中所有胞嘧啶组合的DNA探针，除了CGCAG垂直条GTG中胞嘧啶(5caC)的羧化外，没有任何DNA探针改变结合。5caC增强了所有受试B-HLH同源二聚体和异源二聚体的结合，尤其是Tcf3垂直杆Ascl1异源二聚体，其结合量增加了近10倍。这些结果突出了5mC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。
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 vertical bar 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 vertical bar GTG. 5caC enhanced binding of all examined B-HLH homodimers and heterodimers, particularly the Tcf3 vertical bar Ascl1 heterodimer which increased binding similar to 10-fold. These results highlight a potential function of the oxidative products of 5mC, changing the DNA binding of sequence-specific transcription factors.