Volume 6 Supplement 1

Epigenetics and Chromatin: Interactions and processes

Open Access

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

  • Li Shen1, 2, 3,
  • Hao Wu1, 2, 3, 5,
  • Dinh Diep6,
  • Ana C D’Alessio1, 2, 3,
  • Alan Fung6,
  • Kun Zhang6 and
  • Yi Zhang1, 2, 3, 4
Contributed equally
Epigenetics & Chromatin20136(Suppl 1):P88

DOI: 10.1186/1756-8935-6-S1-P88

Published: 18 March 2013

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.

Notes

Authors’ Affiliations

(1)
Howard Hughes Medical Institute, Harvard Medical School
(2)
Program in Cellular and Molecular Medicine, Boston Children’s Hospital, Harvard Medical School
(3)
Department of Genetics, Harvard Medical School
(4)
Harvard Stem Cell Institute, Harvard Medical School
(5)
Department of Stem Cell and Regenerative Biology, Harvard University
(6)
Departments of Bioengineering, University of California at San Diego

Copyright

© Shen et al; licensee BioMed Central Ltd. 2013

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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