4HP3

Crystal structure of Tet3 in complex with a CpG dsDNA

Summary for 4HP3

• Entry DOI: 10.2210/pdb4hp3/pdb
• Related: 4HP1
• Descriptor: DNA (5'-D(*GP*CP*CP*AP*AP*CP*GP*TP*TP*GP*GP*C)-3'), LOC100036628 protein, UNKNOWN ATOM OR ION, ... (5 entities in total)
• Functional Keywords: cxxc, dna methylation, dna binding protein-dna complex, dna binding protein/dna
• Biological source: XENOPUS (SILURANA) TROPICALIS (WESTERN CLAWED FROG)
• Total number of polymer chains: 3
• Total formula weight: 15887.65

Authors

Chao, X.,Tempel, W.,Bian, C.,Bountra, C.,Arrowsmith, C.H.,Edwards, A.M.,Min, J.,Structural Genomics Consortium (SGC) (deposition date: 2012-10-23, release date: 2012-12-05, Last modification date: 2024-04-03)

Primary citation

Xu, Y.,Xu, C.,Kato, A.,Tempel, W.,Abreu, J.G.,Bian, C.,Hu, Y.,Hu, D.,Zhao, B.,Cerovina, T.,Diao, J.,Wu, F.,He, H.H.,Cui, Q.,Clark, E.,Ma, C.,Barbara, A.,Veenstra, G.J.,Xu, G.,Kaiser, U.B.,Liu, X.S.,Sugrue, S.P.,He, X.,Min, J.,Kato, Y.,Shi, Y.G.
Tet3 CXXC Domain and Dioxygenase Activity Cooperatively Regulate Key Genes for Xenopus Eye and Neural Development.
Cell(Cambridge,Mass.), 151:1200-1213, 2012

PubMed 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.

PubMed: 23217707
DOI: 10.1016/j.cell.2012.11.014

Experimental method

X-RAY DIFFRACTION (2.05 Å)