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

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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.