Nucleic acid modifications with epigenetic significance

Epigenetic modifications influence gene expression without alterations to the underlying nucleic acid sequence. In addition to the well-known 5-methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxycytosine (5caC) have recently been discovered in genomic DNA, which all result from iterative oxidation of 5mC by the TET (Ten-Eleven-Translocate) family of enzymes. Recent studies have proposed the roles of these oxidized cytosines in mediating active demethylation of 5mC. Through affinity-based genome-wide sequencing and oxidation-assisted base-resolution sequencing methods, 5hmC is found to be dynamically regulated during development, and is enriched mainly in distal regulatory elements in human and mouse embryonic cells. Among RNA modifications, N-6-methyladenosine (m(6)A) is a widespread yet poorly studied base modification in mRNA and non-coding RNA. The recent discovery that m(6)A in RNA is the major substrate of the fat mass and obesity associated (FTO) protein draws attention to the potential regulatory functions of reversible RNA methylations, which can be dynamic, and could be important in many fundamental cellular functions.