Document Detail


Tet3 CXXC domain and dioxygenase activity cooperatively regulate key genes for Xenopus eye and neural development.
MedLine Citation:
PMID:  23217707     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
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
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cell     Volume:  151     ISSN:  1097-4172     ISO Abbreviation:  Cell     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-10     Completed Date:  2013-02-06     Revised Date:  2013-12-12    
Medline Journal Info:
Nlm Unique ID:  0413066     Medline TA:  Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1200-13     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
Data Bank Information
Bank Name/Acc. No.:
GENBANK/HQ220207;  HQ220208;  HQ220209;  HQ423151; GEO/GSE41551; PDB/4HP1;  4HP3
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MeSH Terms
Descriptor/Qualifier:
Animals
DNA-Binding Proteins / chemistry,  metabolism
Dioxygenases / chemistry*,  genetics,  metabolism*
Eye / embryology*
Molecular Sequence Data
Neurogenesis*
Promoter Regions, Genetic
Protein Structure, Tertiary
Xenopus Proteins / chemistry*,  genetics,  metabolism*
Xenopus laevis / embryology*,  metabolism
Grant Support
ID/Acronym/Agency:
GM074241/GM/NIGMS NIH HHS; GM078458/GM/NIGMS NIH HHS; GM087641/GM/NIGMS NIH HHS; R01 EY007883/EY/NEI NIH HHS
Chemical
Reg. No./Substance:
0/DNA-Binding Proteins; 0/Xenopus Proteins; EC 1.13.11.-/Dioxygenases; EC 1.13.11.-/TET3 protein, Xenopus
Comments/Corrections

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