Dataset Information


Genome-wide analysis reveals TET- and TDG-mediated 5-methylcytosine oxidation dynamics [MeDIP-Seq]

ABSTRACT: Ten-eleven translocation (Tet) family of DNA dioxygenases converts 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5- carboxylcytosine (5caC) through iterative oxidation reactions. While 5mC and 5hmC are relatively abundant, 5fC and 5caC are at very low levels in the mammalian genome. Thymine DNA glycosylase (TDG) and base excision repair (BER) pathways can actively remove 5fC/5caC to regenerate unmethylated cytosine, but it is unclear to what extent and at which part of the genome such active demethylation processes take place. Here, we have performed high-throughput sequencing analysis of 5mC/5hmC/5fC/5caC- enriched DNA using modification-specific antibodies and generated genome-wide distribution maps of these cytosine modifications in wild-type and Tdg-deficient mouse embryonic stem cells (ESCs). We observe that the steady state 5fC and 5caC are preferentially detected at repetitive sequences in wild-type mouse ESCs. Depletion of TDG causes marked accumulation of 5fC and 5caC at a large number of distal gene regulatory elements and transcriptionally repressed/poised gene promoters, suggesting that Tet/TDG-dependent dynamic cycling of 5mC oxidation states may be involved in regulating the function of these regions. Thus, comprehensive mapping of 5mC oxidation and BER pathway activity in the mammalian genome provides a promising approach for better understanding of biological roles of DNA methylation and demethylation dynamics in development and diseases. In this dataset, we include the DIP-seq data of 5mC, 5hmC, 5fC and 5caC in both control and Tdg knockdown mouse embryonic stem cells.

ORGANISM(S): Mus musculus  

SUBMITTER: Dinh Diep   Li Shen  Ana C D'Alessio  Kun Zhang  Shinpei Yamaguchi  Alan Fung  Yi Zhang  Hao Wu 

PROVIDER: E-GEOD-46111 | ArrayExpress | 2013-04-18



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

Shen Li L   Wu Hao H   Diep Dinh D   Yamaguchi Shinpei S   D'Alessio Ana C AC   Fung Ho-Lim HL   Zhang Kun K   Zhang Yi Y  

Cell 20130418 3

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  ...[more]

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