Genome-wide analysis reveals TET- and TDG-dependent 5-methylcytosine oxidation dynamics.

TitleGenome-wide analysis reveals TET- and TDG-dependent 5-methylcytosine oxidation dynamics.
Publication TypeJournal Article
Year of Publication2013
AuthorsShen L, Wu H, Diep D, Yamaguchi S, D'Alessio AC, Fung H-L, Zhang K, Zhang Y
JournalCell
Volume153
Issue3
Pagination692-706
Date Published2013 Apr 25
ISSN1097-4172
Keywords5-Methylcytosine, Animals, Cytosine, Dioxygenases, DNA Methylation, DNA Repair, Embryonic Stem Cells, Epigenesis, Genetic, Genetic Techniques, Genome-Wide Association Study, Heterochromatin, Mice, Oxidation-Reduction, Regulatory Elements, Transcriptional, Thymine DNA Glycosylase
Abstract

TET dioxygenases successively oxidize 5-methylcytosine (5mC) in mammalian genomes to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). 5fC/5caC can be excised and repaired to regenerate unmodified cytosines by thymine-DNA glycosylase (TDG) and base excision repair (BER) pathway, but it is unclear to what extent and at which part of the genome this active demethylation process takes place. Here, we have generated genome-wide distribution maps of 5hmC/5fC/5caC using modification-specific antibodies in wild-type and Tdg-deficient mouse embryonic stem cells (ESCs). In wild-type mouse ESCs, 5fC/5caC accumulates to detectable levels at major satellite repeats but not at nonrepetitive loci. In contrast, Tdg depletion in mouse ESCs causes marked accumulation of 5fC and 5caC at a large number of proximal and distal gene regulatory elements. Thus, these results reveal the genome-wide view of iterative 5mC oxidation dynamics and indicate that TET/TDG-dependent active DNA demethylation process occurs extensively in the mammalian genome.

DOI10.1016/j.cell.2013.04.002
PubMed URLhttp://www.ncbi.nlm.nih.gov/pubmed/23602152?dopt=Abstract
PMCPMC3687516
Alternate JournalCell
PubMed ID23602152