Tet3 Reads 5-Carboxylcytosine through Its CXXC Domain and Is a Potential Guardian against Neurodegeneration
We report that the mammalian 5-methylcytosine (5mC) oxidase Tet3 exists as three major isoforms and characterized the full-length isoform containing an N-terminal CXXC domain (Tet3FL). This CXXC domain binds to unmethylated CpGs, but, unexpectedly, its highest affinity is toward 5-carboxylcytosine (...
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2016-01-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124715014850 |
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doaj-47abb58ffc4b449a8f329dae7b4c68822020-11-25T02:29:00ZengElsevierCell Reports2211-12472016-01-0114349350510.1016/j.celrep.2015.12.044Tet3 Reads 5-Carboxylcytosine through Its CXXC Domain and Is a Potential Guardian against NeurodegenerationSeung-Gi Jin0Zhi-Min Zhang1Thomas L. Dunwell2Matthew R. Harter3Xiwei Wu4Jennifer Johnson5Zheng Li6Jiancheng Liu7Piroska E. Szabó8Qiang Lu9Guo-liang Xu10Jikui Song11Gerd P. Pfeifer12Center for Epigenetics, Van Andel Research Institute, Grand Rapids, MI 49503, USADepartment of Biochemistry, University of California, Riverside, Riverside, CA 92521, USADepartment of Cancer Biology, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USADepartment of Biochemistry, University of California, Riverside, Riverside, CA 92521, USADepartment of Molecular and Cellular Biology, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USACenter for Epigenetics, Van Andel Research Institute, Grand Rapids, MI 49503, USAThe State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, ChinaDepartment of Neurosciences, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USACenter for Epigenetics, Van Andel Research Institute, Grand Rapids, MI 49503, USADepartment of Neurosciences, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USAThe State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai 200031, ChinaDepartment of Biochemistry, University of California, Riverside, Riverside, CA 92521, USACenter for Epigenetics, Van Andel Research Institute, Grand Rapids, MI 49503, USAWe report that the mammalian 5-methylcytosine (5mC) oxidase Tet3 exists as three major isoforms and characterized the full-length isoform containing an N-terminal CXXC domain (Tet3FL). This CXXC domain binds to unmethylated CpGs, but, unexpectedly, its highest affinity is toward 5-carboxylcytosine (5caC). We determined the crystal structure of the CXXC domain-5caC-DNA complex, revealing the structural basis of the binding specificity of this domain as a reader of CcaCG sequences. Mapping of Tet3FL in neuronal cells shows that Tet3FL is localized precisely at the transcription start sites (TSSs) of genes involved in lysosome function, mRNA processing, and key genes of the base excision repair pathway. Therefore, Tet3FL may function as a regulator of 5caC removal by base excision repair. Active removal of accumulating 5mC from the TSSs of genes coding for lysosomal proteins by Tet3FL in postmitotic neurons of the brain may be important for preventing neurodegenerative diseases.http://www.sciencedirect.com/science/article/pii/S2211124715014850 |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Seung-Gi Jin Zhi-Min Zhang Thomas L. Dunwell Matthew R. Harter Xiwei Wu Jennifer Johnson Zheng Li Jiancheng Liu Piroska E. Szabó Qiang Lu Guo-liang Xu Jikui Song Gerd P. Pfeifer |
| spellingShingle |
Seung-Gi Jin Zhi-Min Zhang Thomas L. Dunwell Matthew R. Harter Xiwei Wu Jennifer Johnson Zheng Li Jiancheng Liu Piroska E. Szabó Qiang Lu Guo-liang Xu Jikui Song Gerd P. Pfeifer Tet3 Reads 5-Carboxylcytosine through Its CXXC Domain and Is a Potential Guardian against Neurodegeneration Cell Reports |
| author_facet |
Seung-Gi Jin Zhi-Min Zhang Thomas L. Dunwell Matthew R. Harter Xiwei Wu Jennifer Johnson Zheng Li Jiancheng Liu Piroska E. Szabó Qiang Lu Guo-liang Xu Jikui Song Gerd P. Pfeifer |
| author_sort |
Seung-Gi Jin |
| title |
Tet3 Reads 5-Carboxylcytosine through Its CXXC Domain and Is a Potential Guardian against Neurodegeneration |
| title_short |
Tet3 Reads 5-Carboxylcytosine through Its CXXC Domain and Is a Potential Guardian against Neurodegeneration |
| title_full |
Tet3 Reads 5-Carboxylcytosine through Its CXXC Domain and Is a Potential Guardian against Neurodegeneration |
| title_fullStr |
Tet3 Reads 5-Carboxylcytosine through Its CXXC Domain and Is a Potential Guardian against Neurodegeneration |
| title_full_unstemmed |
Tet3 Reads 5-Carboxylcytosine through Its CXXC Domain and Is a Potential Guardian against Neurodegeneration |
| title_sort |
tet3 reads 5-carboxylcytosine through its cxxc domain and is a potential guardian against neurodegeneration |
| publisher |
Elsevier |
| series |
Cell Reports |
| issn |
2211-1247 |
| publishDate |
2016-01-01 |
| description |
We report that the mammalian 5-methylcytosine (5mC) oxidase Tet3 exists as three major isoforms and characterized the full-length isoform containing an N-terminal CXXC domain (Tet3FL). This CXXC domain binds to unmethylated CpGs, but, unexpectedly, its highest affinity is toward 5-carboxylcytosine (5caC). We determined the crystal structure of the CXXC domain-5caC-DNA complex, revealing the structural basis of the binding specificity of this domain as a reader of CcaCG sequences. Mapping of Tet3FL in neuronal cells shows that Tet3FL is localized precisely at the transcription start sites (TSSs) of genes involved in lysosome function, mRNA processing, and key genes of the base excision repair pathway. Therefore, Tet3FL may function as a regulator of 5caC removal by base excision repair. Active removal of accumulating 5mC from the TSSs of genes coding for lysosomal proteins by Tet3FL in postmitotic neurons of the brain may be important for preventing neurodegenerative diseases. |
| url |
http://www.sciencedirect.com/science/article/pii/S2211124715014850 |
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