Epigenetic regulations of DNA and histone methylation and deMethylation: Structures and Mechanisms

摘要/摘要 哺乳动物中基因表达的控制部分依赖于DNA中胞嘧啶残基的修饰， 存在至少五种形式：胞嘧啶（C）、5-甲基胞嘧啶（5 mC）、5-羟甲基胞嘧啶（5 hmC）、5-甲基胞嘧啶（5 hm 甲酰胞嘧啶（5 fC）和5-羧基胞嘧啶（5caC）。DNA甲基转移酶在5-位甲基化胞嘧啶 位置，在基因组中产生5 mC。10 - 11易位（泰特）双加氧酶将5 mC转化为5 hmC， 5 fC和5caC在三个连续的氧化反应。这些修改在过程中被动态地调节。 发育和细胞分化。了解这些修饰的功能和监管 控制胞嘧啶的五种形式的水平和基因组分布的机制，我们建议 研究产生，读取和去除这些DNA修饰以及相关的酶/蛋白质 组蛋白甲基化

Summary/Abstract The control of gene expression in mammals relies in part on modifications to cytosine residues in DNA, which exist in at least five forms: cytosine (C), 5-methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC), 5- formylcytosine (5fC) and 5-carboxylcytosine (5caC). DNA methyltransferases methylate cytosine at the 5- position, generating 5mC in the genome. Ten-eleven translocation (Tet) dioxygenases convert 5mC to 5hmC, 5fC, and 5caC in three consecutive oxidation reactions. These modifications are dynamically regulated during development and cell differentiation. To understand the function of these modifications and the regulatory mechanisms that control the levels and genomic distribution of the five forms of the cytosine, we propose to study the enzymes/proteins that generate, read, and remove these DNA modifications as well as associated histone methylation.