Tet-mediated formation of 5-carboxylcytosine and its excision by TDG in mammalian DNA.

Science
Yu-Fei HeGuo-Liang Xu

Abstract

The prevalent DNA modification in higher organisms is the methylation of cytosine to 5-methylcytosine (5mC), which is partially converted to 5-hydroxymethylcytosine (5hmC) by the Tet (ten eleven translocation) family of dioxygenases. Despite their importance in epigenetic regulation, it is unclear how these cytosine modifications are reversed. Here, we demonstrate that 5mC and 5hmC in DNA are oxidized to 5-carboxylcytosine (5caC) by Tet dioxygenases in vitro and in cultured cells. 5caC is specifically recognized and excised by thymine-DNA glycosylase (TDG). Depletion of TDG in mouse embyronic stem cells leads to accumulation of 5caC to a readily detectable level. These data suggest that oxidation of 5mC by Tet proteins followed by TDG-mediated base excision of 5caC constitutes a pathway for active DNA demethylation.

References

Jul 1, 1997·The Biochemical Journal·H E KrokanG Slupphaug
Dec 3, 1999·Science·T Lindahl, R D Wood
Apr 26, 2000·Proceedings of the National Academy of Sciences of the United States of America·B ZhuJ P Jost
Aug 30, 2001·The Journal of Biological Chemistry·R J BoorsteinG W Teebor
Sep 28, 2004·Nature Cell Biology·Stina Simonsson, John Gurdon
Mar 31, 2006·Current Topics in Microbiology and Immunology·C P Walsh, G L Xu
Sep 21, 2006·Journal of the American Chemical Society·Matthew T BennettAlexander C Drohat
Mar 7, 2008·Nature·Raphaël MétivierGilles Salbert
May 12, 2009·Nature Chemical Biology·Zita LiutkeviciuteSaulius Klimasauskas
Aug 5, 2010·Nature Reviews. Molecular Cell Biology·Susan C Wu, Yi Zhang
Feb 16, 2011·Cell Research·Xin-Jian HeJian-Kang Zhu
Feb 18, 2011·Clinica Chimica Acta; International Journal of Clinical Chemistry·Christina DahlPer Guldberg
Apr 15, 2011·Nature·Kristine WilliamsKristian Helin
May 10, 2011·Nature·William A PastorAnjana Rao
Jul 2, 2011·Angewandte Chemie·Toni PfaffenederThomas Carell

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Citations

Nov 4, 2011·Chromosoma·Angelika L Jacobs, Primo Schär
Mar 20, 2012·Chromosoma·Martin Leeb, Anton Wutz
Dec 13, 2012·International Journal of Hematology·Jelena D Milosevic, Robert Kralovics
Jan 30, 2013·International Journal of Hematology·Tomoki Naoe, Hitoshi Kiyoi
Aug 21, 2013·International Journal of Hematology·Steven M Chan, Ravindra Majeti
Oct 1, 2013·Protein & Cell·Tao WangPeng Jin
Oct 24, 2013·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Yi-Lan WengGuo-li Ming
Jan 19, 2013·Sports Medicine·Tobias EhlertDirk A Moser
Jan 24, 2012·Cancer Letters·Ho-Sun Lee, Zdenko Herceg
Sep 27, 2012·Cancer Letters·Igor P Pogribny, Frederick A Beland
Jan 29, 2013·Molecular Aspects of Medicine·Lei LiJurrien Dean
Aug 21, 2013·Neuropharmacology·David P GavinRajiv P Sharma
Sep 3, 2011·Cell Stem Cell·Luisa CimminoIannis Aifantis
Mar 5, 2013·Trends in Biochemical Sciences·Albert Jeltsch
Aug 13, 2013·Trends in Biochemical Sciences·Chun-Xiao Song, Chuan He
Jun 19, 2013·Journal of the American Chemical Society·Ruichuan YinHailin Wang
Aug 29, 2013·Journal of the American Chemical Society·Stefan SchiesserThomas Carell
Jun 14, 2013·Journal of the American Chemical Society·Xingyu LuChuan He
Sep 26, 2013·Journal of the American Chemical Society·Atanu MaitiAlexander C Drohat
Aug 25, 2011·Cell Research·Zhizhong Gong, Jian-Kang Zhu
Aug 8, 2012·Cell Research·Jinsuk KangAnjana Rao
Jun 7, 2013·Journal of Human Genetics·Takashi Kohda
May 31, 2013·Journal of Human Genetics·Hongbo Zhao, Taiping Chen
Nov 16, 2012·Nature·Shinpei YamaguchiYi Zhang
Oct 25, 2013·Nature·Rahul M Kohli, Yi Zhang
Nov 10, 2012·Nature Biotechnology·Chun-Xiao SongChuan He
Jul 10, 2012·Nature Chemical Biology·Christopher S NabelRahul M Kohli
Feb 14, 2012·Nature Chemical Biology·Liang ZhangChuan He
May 10, 2012·Nature Communications·Michael T BockerAchim Breiling
Jun 14, 2013·Nature Communications·Haiyun GanFuchou Tang
Jul 19, 2013·Nature Communications·Paul GuilhamonStephan Beck
Oct 29, 2013·Nature Genetics·Jiekai ChenDuanqing Pei
Nov 26, 2013·Nature Genetics·Mira JeongMargaret A Goodell
Jul 23, 2013·Nature Immunology·Silvia Monticelli, Gioacchino Natoli
Jul 12, 2012·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Lisa D MooreGuoping Fan

❮ Previous
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