TET-catalyzed 5-methylcytosine hydroxylation is dynamically regulated by metabolites
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Dear Editor,DNA methylation suppresses gene expression and plays a broad and important role in diverse biological processes such as development and rumor suppression ”1,2”.DNA methylation is generally thought to be relatively stable and heritable.This view is recently changed by the discovery of TET (ten-eleven translocation) family of dioxygenases which catalyze three sequential oxidation reactions:converting 5mC first to 5hmC,and then 5-formylcytosine (5fC),and finally 5-carboxylcytosine (5caC) ”3-7”.A subsequent decarboxylation of 5caC could then lead to DNA demethylation ”3”.While the biological function and catalytic mechanism of TET enzymes are being extensively investigated,much less is currently known about their regulation.
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This work was supported by the National Basic Research Program of China 973 Program; 2012CB910303,2012CB910101,2011CB910600 and 2009CB918401,the Innovation Program of Shanghai Municipal Education Commission 12ZZ008,and the Scholarship Award for Excellent Doctoral Student granted by the Ministry of Education JFH1340003.This work was also supported by NIH grants CA163834 to YX and R01CA108941 to KLG,and Samuel Waxman Foundation to YX.