Tet3 CXXC domain and dioxygenase activity cooperatively regulate key genes for Xenopus eye and neural development.
Tet3 CXXC domain and dioxygenase activity cooperatively regulate key genes for Xenopus eye and neural development.
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DOI：
10.1016/j.cell.2012.11.014
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发表时间：
2012-12-07
期刊：
影响因子：
64.5
通讯作者：
Shi YG
中科院分区：
文献类型：
--
作者：
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
双加氧酶10-11易位家族为DNA甲基化提供了一种新的动态调节机制，并与细胞系分化和肿瘤的发生有关。然而，它们在基因调控和胚胎发育中的功能作用和作用机制在很大程度上是未知的。在这里，我们报道非洲爪哇Tet3通过直接调控一组关键的发育基因，在早期眼睛和神经发育中发挥重要作用。Tet3是一种活性的5mC羟基酶，调节靶基因启动子上的5mC/5hmC状态。生化和结构研究进一步揭示了Tet3 CXXC结构域的一种新的DNA结合模式，该模式对特异性Tet3靶向至关重要。最后，我们证明了酶活性和CXXC结构域是Tet3‘S生物学功能的关键。综上所述，这些发现将Tet3定义为一个新的转录因子，并揭示了Tet3的5mC羟基酶和DNA结合活性协同调控靶基因表达和胚胎发育的分子机制。
Ten-Eleven Translocation (Tet) family of dioxygenases offers a new mechanism for dynamic regulation of DNA methylation and has been implicated in cell lineage differentiation and oncogenesis. Yet their functional roles 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 reveal a novel DNA binding mode of the Tet3 CXXC domain that is critical for specific Tet3 targeting. Finally, we show that the enzymatic activity and CXXC domain are crucial for Tet3’s biological function. Together, these findings define Tet3 as a novel transcription factor 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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影响因子：
3.7
作者：
Globisch D;Münzel M;Müller M;Michalakis S;Wagner M;Koch S;Brückl T;Biel M;Carell T
通讯作者：
Carell T
影响因子：
30.8
作者：
Langemeijer, Saskia M. C.;Kuiper, Roland P.;Jansen, Joop H.
通讯作者：
Jansen, Joop H.
影响因子：
50.3
作者：
Moran-Crusio K;Reavie L;Shih A;Abdel-Wahab O;Ndiaye-Lobry D;Lobry C;Figueroa ME;Vasanthakumar A;Patel J;Zhao X;Perna F;Pandey S;Madzo J;Song C;Dai Q;He C;Ibrahim S;Beran M;Zavadil J;Nimer SD;Melnick A;Godley LA;Aifantis I;Levine RL
通讯作者：
Levine RL
DOI：
10.1126/science.1170116
发表时间：
2009-05-15
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Tahiliani M;Koh KP;Shen Y;Pastor WA;Bandukwala H;Brudno Y;Agarwal S;Iyer LM;Liu DR;Aravind L;Rao A
通讯作者：
Rao A
影响因子：
2.9
作者：
Pradhan, Mihika;Esteve, Pierre-Olivier;Pradhan, Sriharsa
通讯作者：
Pradhan, Sriharsa