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Originally published in Science Express on 16 April 2009
Science 15 May 2009:
Vol. 324. no. 5929, pp. 930 - 935
DOI: 10.1126/science.1170116
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Reports

Conversion of 5-Methylcytosine to 5-Hydroxymethylcytosine in Mammalian DNA by MLL 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 Rao1,*

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 embryonic stem cells, and hmC levels decrease upon RNA interference–mediated depletion of TET1. Thus, TET proteins have potential roles in epigenetic regulation through modification of 5mC to hmC.

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. E-mail: arao{at}idi.harvard.edu (A.R.); aravind{at}ncbi.nlm.nih.gov (L.A.); drliu{at}fas.harvard.edu (D.R.L.)

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