Premium
Dynamic regulation of DNA methylation
Author(s) -
Zhu Bing
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.403.1
Subject(s) - 5 hydroxymethylcytosine , chromatin , 5 methylcytosine , dna demethylation , dna methylation , epigenetics , dna , microbiology and biotechnology , demethylation , biology , methylation , dna binding protein , binding site , chemistry , transcription factor , genetics , gene , gene expression
TET family enzymes successively oxidize 5‐methylcytosine (5mC) to 5‐hydroxymethylcytosine (5hmC), 5‐formylcytosine (5fC) and 5‐carboxylcytosine (5caC), which may lead to eventual demethylation. 5hmC and TET proteins occupy distinct chromatin regions, suggesting unknown mechanisms controlling the fate of 5hmC at different chromatin regions. We report the identification of 5hmC binding proteins displaying preferential association with 5hmC in vitro . In mouse ESCs, the majority of these 5hmC binding proteins localize at distal regulatory regions and their chromatin association is largely TET1 dependent. Interestingly, their binding sites are generally depleted for 5hmC but enriched for 5caC. Knockout of the 5hmC binding protein results in an ectopic accumulation of 5hmC at the original binding sites, which suggests its stimulatory role in facilitating further oxidation of 5hmC at distal regulatory regions. Moreover, at these sites, the main enzyme responsible for further oxidation of 5hmC appears to be TET2, suggesting a stepwise regulation process for 5mC oxidation.