Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Published Online April 16, 2009
Science DOI: 10.1126/science.1170116

Reports

Submitted on December 22, 2008
Accepted on April 3, 2009

Conversion of 5-Methylcytosine to 5-Hydroxymethylcytosine in Mammalian DNA by the MLL Fusion Partner TET1

Mamta Tahiliani 1, Kian Peng Koh 1, Yinghua Shen 2, William A. Pastor 1, Hozefa Bandukwala 1, Yevgeny Brudno 2, Suneet Agarwal 3, Lakshminarayan M. Iyer 4, David R. Liu 2*, L. Aravind 4*, Anjana Rao 1*

1 Department of Pathology, Harvard Medical School and Immune Disease Institute, 200 Longwood Avenue, Boston, MA 02115, USA.
2 Department of Chemistry and Chemical Biology and the Howard Hughes Medical Institute, Harvard University, Cambridge, MA 02138, USA.
3 Division of Pediatric Hematology/Oncology, Children’s Hospital Boston and Dana-Farber Cancer Institute, Boston, MA 02115, USA.
4 National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA.

* To whom correspondence should be addressed.
David R. Liu , E-mail: drliu{at}fas.harvard.edu
L. Aravind , E-mail: aravind{at}ncbi.nlm.nih.gov
Anjana Rao , E-mail: arao{at}idi.harvard.edu

DNA cytosine methylation is crucial for retrotransposon silencing and mammalian development. In a computational search for enzymes that could modify 5-methylcytosine (5mC), we identified TET proteins as mammalian homologs of the trypanosome proteins JBP1 and JBP2, which have been proposed to oxidize the 5-methyl group of thymine. We show here that TET1, a fusion partner of the MLL gene in acute myeloid leukemia, is a 2-oxoglutarate (2OG)- and Fe(II)-dependent enzyme that catalyzes conversion of 5mC to 5-hydroxymethylcytosine (hmC) in cultured cells and in vitro. hmC is present in the genome of mouse ES cells, and hmC levels decrease upon RNAi-mediated depletion of TET1. Thus, TET proteins have potential roles in epigenetic regulation through modification of 5mC to hmC.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Differential binding of Escherichia coli McrA protein to DNA sequences that contain the dinucleotide m5CpG.
E. A. Mulligan, E. Hatchwell, S. R. McCorkle, and J. J. Dunn (2009)
Nucleic Acids Res.
   Abstract »    Full Text »    PDF »
Getting to grips with DNA methylation.
R. R. Meehan (2009)
Development 136, 4074-4075
   Full Text »    PDF »
Molecular basis of myelodysplastic/myeloproliferative neoplasms.
A. Reiter, R. Invernizzi, N. C.P. Cross, and M. Cazzola (2009)
Haematologica 94, 1634-1638
   Full Text »    PDF »
TET2 gene mutation is a frequent and adverse event in chronic myelomonocytic leukemia.
O. Kosmider, V. Gelsi-Boyer, M. Ciudad, C. Racoeur, V. Jooste, N. Vey, B. Quesnel, P. Fenaux, J.-N. Bastie, O. Beyne-Rauzy, et al. (2009)
Haematologica 94, 1676-1681
   Abstract »    Full Text »    PDF »
TET2 mutation is an independent favorable prognostic factor in myelodysplastic syndromes (MDSs).
O. Kosmider, V. Gelsi-Boyer, M. Cheok, S. Grabar, V. Della-Valle, F. Picard, F. Viguie, B. Quesnel, O. Beyne-Rauzy, E. Solary, et al. (2009)
Blood 114, 3285-3291
   Abstract »    Full Text »    PDF »
Genomic imprinting: employing and avoiding epigenetic processes.
M. S. Bartolomei (2009)
Genes & Dev. 23, 2124-2133
   Abstract »    Full Text »    PDF »
Analysis of the Ten-Eleven Translocation 2 (TET2) gene in familial myeloproliferative neoplasms.
C. Saint-Martin, G. Leroy, F. Delhommeau, G. Panelatti, S. Dupont, C. James, I. Plo, D. Bordessoule, C. Chomienne, A. Delannoy, et al. (2009)
Blood 114, 1628-1632
   Abstract »    Full Text »    PDF »
Mammalian cytosine methylation at a glance.
S. K. T. Ooi, A. H. O'Donnell, and T. H. Bestor (2009)
J. Cell Sci. 122, 2787-2791
   Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)