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
{"title":"Tet3 CXXC结构域和二氧酶活性协同调控章鱼眼睛和神经发育的关键基因。","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","doi":"10.1016/j.cell.2012.11.014","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":45,"journal":{"name":"Journal of Chemical Theory and Computation","volume":" ","pages":"1200-13"},"PeriodicalIF":5.7000,"publicationDate":"2012-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3705565/pdf/nihms423101.pdf","citationCount":"0","resultStr":"{\"title\":\"Tet3 CXXC domain and dioxygenase activity cooperatively regulate key genes for Xenopus eye and neural 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\",\"doi\":\"10.1016/j.cell.2012.11.014\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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.</p>\",\"PeriodicalId\":45,\"journal\":{\"name\":\"Journal of Chemical Theory and Computation\",\"volume\":\" \",\"pages\":\"1200-13\"},\"PeriodicalIF\":5.7000,\"publicationDate\":\"2012-12-07\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3705565/pdf/nihms423101.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Chemical Theory and Computation\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1016/j.cell.2012.11.014\",\"RegionNum\":1,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CHEMISTRY, PHYSICAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Chemical Theory and Computation","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.cell.2012.11.014","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, PHYSICAL","Score":null,"Total":0}
Tet3 CXXC domain and dioxygenase activity cooperatively regulate key genes for Xenopus eye and neural development.
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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The Journal of Chemical Theory and Computation invites new and original contributions with the understanding that, if accepted, they will not be published elsewhere. Papers reporting new theories, methodology, and/or important applications in quantum electronic structure, molecular dynamics, and statistical mechanics are appropriate for submission to this Journal. Specific topics include advances in or applications of ab initio quantum mechanics, density functional theory, design and properties of new materials, surface science, Monte Carlo simulations, solvation models, QM/MM calculations, biomolecular structure prediction, and molecular dynamics in the broadest sense including gas-phase dynamics, ab initio dynamics, biomolecular dynamics, and protein folding. The Journal does not consider papers that are straightforward applications of known methods including DFT and molecular dynamics. The Journal favors submissions that include advances in theory or methodology with applications to compelling problems.
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