Tet3 CXXC Domain and Dioxygenase Activity Cooperatively Regulate Key Genes for Xenopus Eye and Neural Development

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2012 Dec 11

PMID 23217707

Citations 131

Authors

Yufei Xu

Chao Xu

Akiko Kato

Wolfram Tempel

Jose Garcia Abreu

Chuanbing Bian

Yeguang Hu

Di Hu

Bin Zhao

Tanja Cerovina

Jianbo Diao

Feizhen Wu

Housheng Hansen He

Qingyan Cui

Erin Clark

Chun Ma

Andrew Barbara

Gert Jan C Veenstra

Guoliang Xu

Ursula B Kaiser

X Shirley Liu

Stephen P Sugrue

Xi He

Jinrong Min

Yoichi Kato

Yujiang Geno Shi

Affiliations

Soon will be listed here.

Abstract

Ten-Eleven Translocation (Tet) family of dioxygenases dynamically regulates DNA methylation and has been implicated in cell lineage differentiation and oncogenesis. Yet their functions and mechanisms of action in gene regulation and embryonic development are largely unknown. Here, we report that Xenopus Tet3 plays an essential role in early eye and neural development by directly regulating a set of key developmental genes. Tet3 is an active 5mC hydroxylase regulating the 5mC/5hmC status at target gene promoters. Biochemical and structural studies further demonstrate that the Tet3 CXXC domain is critical for specific Tet3 targeting. Finally, we show that the enzymatic activity and CXXC domain are both crucial for Tet3's biological function. Together, these findings define Tet3 as a transcription regulator and reveal a molecular mechanism by which the 5mC hydroxylase and DNA binding activities of Tet3 cooperate to control target gene expression and embryonic development.

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