State Key Laboratory of Elemento-Organic Chemistry and Department of Chemical Biology, College of Chemistry, Nankai University , Tianjin 300071, China.
Department of Chemistry, Johns Hopkins University , 3400 North Charles Street, Baltimore, Maryland 21218, United States.
J Am Chem Soc. 2017 Aug 9;139(31):10617-10620. doi: 10.1021/jacs.7b05495. Epub 2017 Jul 25.
In situ generation of 5-formylcytosine (5fC) in nucleosome core particles (NCPs) reveals that 5fC leads to essential DNA-protein cross-links (DPCs). Mechanistic studies using chemical models and mutated histones demonstrate that DPCs form reversibly between the formyl function of 5fC and primary amines on histones. These results suggest that DPC formation from 5fC in chromatin occurs in addition to its role in DNA demethylation.
在核小体核心颗粒(NCPs)中原位生成 5-甲酰胞嘧啶(5fC)表明,5fC 导致必需的 DNA-蛋白质交联(DPC)。使用化学模型和突变组蛋白进行的机制研究表明,DPC 可以在 5fC 的甲酰功能和组蛋白上的伯胺之间可逆形成。这些结果表明,DPC 的形成除了在 DNA 去甲基化中的作用外,还可以从染色质中的 5fC 中形成。