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

被引：4259

作者：

Tahiliani, Mamta ^{[3
,4
]}

Koh, Kian Peng ^{[3
,4
]}

Shen, Yinghua ^{[1
,2
]}

Pastor, William A. ^{[3
,4
]}

Bandukwala, Hozefa ^{[3
,4
]}

Brudno, Yevgeny ^{[1
,2
]}

Agarwal, Suneet ^{[5
,6
]}

Iyer, Lakshminarayan M. ^{[7
]}

Liu, David R. ^{[1
,2
]}

Aravind, L. ^{[7
]}

Rao, Anjana ^{[3
,4
]}

机构：

[1] Harvard Univ, Dept Chem & Biol Chem, Cambridge, MA 02138 USA

[2] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA

[3] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA

[4] Immune Dis Inst, Boston, MA 02115 USA

[5] Childrens Hosp Boston, Div Pediat Hematol Oncol, Boston, MA 02115 USA

[6] Dana Farber Canc Inst, Boston, MA 02115 USA

[7] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA

来源：

SCIENCE | 2009年 / 324卷 / 5929期

关键词：

ACUTE MYELOID-LEUKEMIA; GLYCOSYLASE ACTIVITY; CXXC DOMAIN; BASE-J; DEMETHYLATION; CYTOSINE; METHYLATION; PROTEIN; METHYLTRANSFERASE; T(10/11)(Q22; Q23);

D O I：

10.1126/science.1170116

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：930 / 935

页数：6

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