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| | ==Crystal structure of Tet3 in complex with a non-CpG dsDNA== | | ==Crystal structure of Tet3 in complex with a non-CpG dsDNA== |
| - | <StructureSection load='4hp1' size='340' side='right' caption='[[4hp1]], [[Resolution|resolution]] 2.25Å' scene=''> | + | <StructureSection load='4hp1' size='340' side='right'caption='[[4hp1]], [[Resolution|resolution]] 2.25Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4hp1]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Xenopus_(silurana)_tropicalis Xenopus (silurana) tropicalis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HP1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4HP1 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4hp1]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Xenopus_tropicalis Xenopus tropicalis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4HP1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4HP1 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.25Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=5CM:5-METHYL-2-DEOXY-CYTIDINE-5-MONOPHOSPHATE'>5CM</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5CM:5-METHYL-2-DEOXY-CYTIDINE-5-MONOPHOSPHATE'>5CM</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4hp3|4hp3]]</td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4hp1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hp1 OCA], [https://pdbe.org/4hp1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4hp1 RCSB], [https://www.ebi.ac.uk/pdbsum/4hp1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4hp1 ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">tet3, LOC100036628 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=8364 Xenopus (Silurana) tropicalis])</td></tr>
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| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4hp1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4hp1 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4hp1 RCSB], [http://www.ebi.ac.uk/pdbsum/4hp1 PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| - | <div style="background-color:#fffaf0;">
| + | == Function == |
| - | == Publication Abstract from PubMed == | + | [https://www.uniprot.org/uniprot/TET3_XENTR TET3_XENTR] Dioxygenase that catalyzes the conversion of the modified genomic base 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC) and plays a key role in epigenetic chromatin reprogramming during embryonic development. Conversion of 5mC into 5hmC probably constitutes the first step in cytosine demethylation. Selectively binds to the promoter region of target genes and contributes to regulate the expression of numerous developmental genes, including pax6, rax, sox9 and six3. May also contribute to the regulation of target genes in ways that do not require its enzyme activity.<ref>PMID:23217707</ref> |
| - | 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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| - | 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 Cell. 2012 Dec 7;151(6):1200-13. doi: 10.1016/j.cell.2012.11.014. PMID:23217707<ref>PMID:23217707</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
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| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Arrowsmith, C H]] | + | [[Category: Large Structures]] |
| - | [[Category: Bian, C]] | + | [[Category: Xenopus tropicalis]] |
| - | [[Category: Bountra, C]] | + | [[Category: Arrowsmith CH]] |
| - | [[Category: Chao, X]] | + | [[Category: Bian C]] |
| - | [[Category: Edwards, A M]] | + | [[Category: Bountra C]] |
| - | [[Category: Min, J]] | + | [[Category: Chao X]] |
| - | [[Category: Structural genomic]] | + | [[Category: Edwards AM]] |
| - | [[Category: Tempel, W]] | + | [[Category: Min J]] |
| - | [[Category: Cxxc]] | + | [[Category: Tempel W]] |
| - | [[Category: Dna binding protein-dna complex]]
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| - | [[Category: Dna methylation]]
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| - | [[Category: Sgc]]
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| Structural highlights
Function
TET3_XENTR Dioxygenase that catalyzes the conversion of the modified genomic base 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC) and plays a key role in epigenetic chromatin reprogramming during embryonic development. Conversion of 5mC into 5hmC probably constitutes the first step in cytosine demethylation. Selectively binds to the promoter region of target genes and contributes to regulate the expression of numerous developmental genes, including pax6, rax, sox9 and six3. May also contribute to the regulation of target genes in ways that do not require its enzyme activity.[1]
References
- ↑ 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. Tet3 CXXC Domain and Dioxygenase Activity Cooperatively Regulate Key Genes for Xenopus Eye and Neural Development. Cell. 2012 Dec 7;151(6):1200-13. doi: 10.1016/j.cell.2012.11.014. PMID:23217707 doi:http://dx.doi.org/10.1016/j.cell.2012.11.014
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