Reversing DNA methylation: mechanisms, genomics, and biological functions

Cell. 2014 Jan 16;156(1-2):45-68. doi: 10.1016/j.cell.2013.12.019.


Methylation of cytosines in the mammalian genome represents a key epigenetic modification and is dynamically regulated during development. Compelling evidence now suggests that dynamic regulation of DNA methylation is mainly achieved through a cyclic enzymatic cascade comprised of cytosine methylation, iterative oxidation of methyl group by TET dioxygenases, and restoration of unmodified cytosines by either replication-dependent dilution or DNA glycosylase-initiated base excision repair. In this review, we discuss the mechanism and function of DNA demethylation in mammalian genomes, focusing particularly on how developmental modulation of the cytosine-modifying pathway is coupled to active reversal of DNA methylation in diverse biological processes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5-Methylcytosine / metabolism
  • Animals
  • DNA Methylation*
  • Genome
  • Humans
  • Oxidoreductases, N-Demethylating / metabolism*
  • Promoter Regions, Genetic


  • 5-Methylcytosine
  • Oxidoreductases, N-Demethylating