Biochemistry. 2020 Sep 29;59(38):3529-3540. doi: 10.1021/acs.biochem.0c00475. Epub 2020 Sep 20.
In mammalian cells, 5-methylcytosine (5mC) occurs in genomic double-stranded DNA (dsDNA) and is enzymatically oxidized to 5-hydroxymethylcytosine (5hmC), then to 5-formylcytosine (5fC), and finally to 5-carboxylcytosine (5caC). These cytosine modifications are enriched in regulatory regions of the genome. The effect of these oxidative products on five bZIP dimers (CREB1, ATF2, Zta, ATF3|cJun, and cFos|cJun) binding to five types of dsDNA was measured using protein binding microarrays. The five dsDNAs contain either cytosine in both DNA strands or cytosine in one strand and either 5mC, 5hmC, 5fC, or 5caC in the second strand. Some sequences containing the CEBP half-site GCAA are bound more strongly by all five bZIP domains when dsDNA contains 5mC, 5hmC, or 5fC. dsDNA containing 5caC in some TRE (AP-1)-like sequences, e.g., TGACTAA, is better bound by Zta, ATF3|cJun, and cFos|cJun.
在哺乳动物细胞中，5-甲基胞嘧啶（5mC）存在于基因组双链 DNA（dsDNA）中，并被酶氧化为 5-羟甲基胞嘧啶（5hmC），然后是 5-甲酰基胞嘧啶（5fC），最后是 5-羧基胞嘧啶（5caC）。这些胞嘧啶修饰在基因组的调控区域中富集。使用蛋白质结合微阵列测量了这些氧化产物对五个 bZIP 二聚体（CREB1、ATF2、Zta、ATF3|cJun 和 cFos|cJun）与五种类型 dsDNA 结合的影响。五种 dsDNA 要么两条 DNA 链上都有胞嘧啶，要么一条 DNA 链上有胞嘧啶，另一条 DNA 链上有 5mC、5hmC、5fC 或 5caC。一些包含 CEBP 半位点 GCAA 的序列，当 dsDNA 含有 5mC、5hmC 或 5fC 时，所有五个 bZIP 结构域的结合更紧密。在一些 TRE（AP-1）样序列（例如 TGACTAA）中，dsDNA 中含有 5caC，Zta、ATF3|cJun 和 cFos|cJun 的结合更好。
