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Tahiliani, Mamta; Koh, Kian Peng; Shen, Yinghua; Pastor, William A; Bandukwala, Hozefa; Brudno, Yevgeny; Agarwal, Suneet; Iyer, Lakshminarayan M; Liu, David R; Aravind, L; Rao, Anjana
Science (American Association for the Advancement of Science), 05/2009, Letnik: 324, Številka: 5929Journal Article
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.
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