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Cell 2012 Dec 07;1516:1200-13. doi: 10.1016/j.cell.2012.11.014.
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Tet3 CXXC domain and dioxygenase activity cooperatively regulate key genes for Xenopus eye and neural development.

Xu Y , Xu C , Kato A , Tempel W , Abreu JG , Bian C , Hu Y , Hu D , Zhao B , Cerovina T , Diao J , Wu F , He HH , Cui Q , Clark E , Ma C , Barbara A , Veenstra GJ , Xu G , Kaiser UB , Liu XS , Sugrue SP , He X , Min J , Kato Y , Shi YG .

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 ID: 23217707
PMC ID: PMC3705565
Article link: Cell
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: actc1 avd cpa1 gal.2 kit neurog2 odc1 otx2 pax6 rax shh six3 snai1 sox2 sox9 tet3 tubb2b
Morpholinos: tet3 MO1 tet3 MO2

Article Images: [+] show captions
References [+] :
Allen, Solution structure of the nonmethyl-CpG-binding CXXC domain of the leukaemia-associated MLL histone methyltransferase. 2006, Pubmed