Tet Proteins Can Convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine

Overview

Journal Science

Specialty Science

Date 2011 Jul 23

PMID 21778364

Citations 1680

Authors

Shinsuke Ito

Li Shen

Qing Dai

Susan C Wu

Leonard B Collins

James A Swenberg

Chuan He

Yi Zhang

Affiliations

Soon will be listed here.

Abstract

5-methylcytosine (5mC) in DNA plays an important role in gene expression, genomic imprinting, and suppression of transposable elements. 5mC can be converted to 5-hydroxymethylcytosine (5hmC) by the Tet (ten eleven translocation) proteins. Here, we show that, in addition to 5hmC, the Tet proteins can generate 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) from 5mC in an enzymatic activity-dependent manner. Furthermore, we reveal the presence of 5fC and 5caC in genomic DNA of mouse embryonic stem cells and mouse organs. The genomic content of 5hmC, 5fC, and 5caC can be increased or reduced through overexpression or depletion of Tet proteins. Thus, we identify two previously unknown cytosine derivatives in genomic DNA as the products of Tet proteins. Our study raises the possibility that DNA demethylation may occur through Tet-catalyzed oxidation followed by decarboxylation.

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