PMID: 21896958Sep 8, 2011Paper

Global 5-hydroxymethylcytosine content is significantly reduced in tissue stem/progenitor cell compartments and in human cancers

Michael C HaffnerSrinivasan Yegnasubramanian


DNA methylation at the 5-position of cytosines (5 mC) represents an important epigenetic modification involved in tissue differentiation and is frequently altered in cancer. Recent evidence suggests that 5 mC can be converted to 5-hydroxymethylcytosine (5 hmC) in an enzymatic process involving members of the TET protein family. Such 5 hmC modifications are known to be prevalent in DNA of embryonic stem cells and in the brain, but the distribution of 5 hmC in the majority of embryonic and adult tissues has not been rigorously explored. Here, we describe an immunohistochemical detection method for 5 hmC and the application of this technique to study the distribution of 5 hmC in a large set of mouse and human tissues. We found that 5 hmC was abundant in the majority of embryonic and adult tissues. Additionally, the level of 5 hmC closely tracked with the differentiation state of cells in hierarchically organized tissues. The highest 5 hmC levels were observed in terminally differentiated cells, while less differentiated tissue stem/progenitor cell compartments had very low 5 hmC levels. Furthermore, 5 hmC levels were profoundly reduced in carcinoma of the prostate, breast and colon compared to normal tissues. Our findings suggest ...Continue Reading


May 26, 1976·Journal of Molecular Evolution·R M Kothari, V Shankar
May 1, 1989·The American Journal of Surgical Pathology·L Hedrick, J I Epstein
Feb 1, 1972·The Biochemical Journal·N W PennR Yura
Nov 13, 2004·Cancer Biology & Therapy·Kesmic JacksonMelanie Ehrlich
Sep 9, 2006·Science·Tobias SjöblomVictor E Velculescu
Feb 27, 2007·Cell·Peter A Jones, Stephen B Baylin
Oct 13, 2007·Science·Laura D WoodBert Vogelstein
Mar 14, 2008·The New England Journal of Medicine·Manel Esteller
Jun 10, 2008·Current Opinion in Hematology·Mariusz Z Ratajczak
Jul 1, 2008·Cell·Steen K T Ooi, Timothy H Bestor
Sep 24, 2008·Annual Review of Physiology·Laurens G van der Flier, Hans Clevers
Apr 18, 2009·Science·Skirmantas Kriaucionis, Nathaniel Heintz
Jun 13, 2009·Endocrinology·William G NelsonSrinivasan Yegnasubramanian
Oct 1, 2009·Nature Reviews. Genetics·Peter A Jones, Gangning Liang
Jul 30, 2010·Nature·Zhengyan KanSomasekar Seshagiri
Dec 9, 2010·Nature Reviews. Urology·Angelo M De MarzoSrinivasan Yegnasubramanian
Feb 11, 2011·Nature·Michael F BergerLevi A Garraway
Feb 16, 2011·Proceedings of the National Academy of Sciences of the United States of America·Khursheed IqbalPiroska E Szabó
Apr 2, 2011·The Journal of Biological Chemistry·Zhao-xia Chen, Arthur D Riggs
Apr 15, 2011·Nature·Kristine WilliamsKristian Helin
May 3, 2011·PloS One·Eiji SunamiDave S B Hoon
May 10, 2011·Nature·William A PastorAnjana Rao
Jul 7, 2011·PloS One·Carina FrauerHeinrich Leonhardt


Feb 9, 2012·DNA and Cell Biology·Hasan A Irier, Peng Jin
Feb 16, 2012·Journal of Applied Toxicology : JAT·Tsu-Fan ChengKristi Muldoon-Jacobs
Oct 16, 2012·The Journal of Urology·Antoinette S Perry
Apr 30, 2013·Briefings in Functional Genomics·Benjamin Delatte, François Fuks
May 30, 2013·Proceedings of the National Academy of Sciences of the United States of America·Miao SunMarsha R Rosner
Jul 3, 2013·Proceedings of the National Academy of Sciences of the United States of America·Hao HuangJianjun Chen
Sep 4, 2013·The Prostate·N A DamaschkeD F Jarrard
Mar 19, 2014·Nucleic Acids Research·Asgar Abbas KazraniMatthias Bochtler
Aug 26, 2014·In Vitro Cellular & Developmental Biology. Animal·Pranapda AumsuwanAsok K Dasmahapatra
Jul 1, 2014·Laboratory Investigation; a Journal of Technical Methods and Pathology·Jonathan J LeeChristine G Lian
Jun 1, 2014·Critical Reviews in Clinical Laboratory Sciences·Dimo DietrichGlen Kristiansen
Nov 29, 2014·Epigenomics·Euan J RodgerIan M Morison
May 13, 2014·Cell and Tissue Research·Gerd P PfeiferSeung-Gi Jin
May 20, 2014·Oncogene·F Valdés-Mora, S J Clark
Apr 3, 2015·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Silvia UdaliSimonetta Friso
Apr 2, 2015·Archives of Gynecology and Obstetrics·Li-Ying ZhangXin-Chen Zhang
Apr 9, 2015·Genome Biology·Santiago Uribe-LewisAdele Murrell
Mar 15, 2016·Clinical Epigenetics·Elham BarazeghiGunnar Westin
May 31, 2017·Nature Reviews. Genetics·Xiaoji Wu, Yi Zhang
Aug 10, 2017·Frontiers in Pharmacology·Wenyong LongQing Liu
Sep 24, 2017·Angewandte Chemie·Thomas CarellFabio Spada
Jun 8, 2018·Human Molecular Genetics·Agustin F FernandezMario F Fraga
Nov 1, 2015·Melanoma Management·Weimin GuoChristine G Lian
Dec 7, 2018·Critical Reviews in Food Science and Nutrition·Dieuwertje E KokEllen Kampman
Jan 19, 2020·Scientific Reports·Santiago Uribe-LewisAdele Murrell
Feb 6, 2020·Current Environmental Health Reports·Joseph Kochmanski, Alison I Bernstein
Jan 12, 2012·International Journal of Cancer. Journal International Du Cancer·Theo F J KrausHans A Kretzschmar

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