title: Emerging roles of TET proteins and 5-hydroxymethylcytosines in active DNA demethylation and beyond.
abstract: Cytosine methylation is the major epigenetic modification of metazoan DNA. Although there is strong evidence that active DNA demethylation occurs in animal cells, the molecular details of this process are unknown. The recent discovery of the TET protein family (TET1-3) 5-methylcytosine hydroxylases has provided a new entry point to reveal the identity of the long-sought DNA demethylase. Here, we review the recent progress in understanding the function of TET proteins and 5-hydroxymethylcytosine (5hmC) through various biochemical and genomic approaches, the current evidence for a role of 5hmC as an early intermediate in active DNA demethylation and the potential functions of TET proteins and 5hmC beyond active DNA demethylation. We also discuss how future studies can extend our knowledge of this novel epigenetic modification.
authors.affiliation: Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Junjie U
authors.initials: JU
authors.lastname: Guo
authors.forename: Yijing
authors.initials: Y
authors.lastname: Su
authors.forename: Chun
authors.initials: C
authors.lastname: Zhong
authors.forename: Guo-li
authors.initials: GL
authors.lastname: Ming
authors.forename: Hongjun
authors.initials: H
authors.lastname: Song
mesh_terms: D044503:5-Methylcytosine / Q000031:analogs & derivatives; D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism; D003596:Cytosine / Q000031:analogs & derivatives* / Q000378:metabolism; D019175:DNA Methylation / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism*; D049308:Dioxygenases; D006801:Humans; D006899:Mixed Function Oxygenases; D009687:Nuclear Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D000097642:GADD45 Proteins
chemical_list: D044503:5-Methylcytosine; D018797:Cell Cycle Proteins; D003596:Cytosine; D004268:DNA-Binding Proteins; D049308:Dioxygenases; D006899:Mixed Function Oxygenases; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C439070:GADD45A protein, human; D000097642:GADD45 Proteins; C011865:5-hydroxymethylcytosine; C462539:TET1 protein, human; C541081:TET2 protein, human