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| ==Mouse ZFP57 zinc fingers in complex with methylated DNA== | | ==Mouse ZFP57 zinc fingers in complex with methylated DNA== |
- | <StructureSection load='4gzn' size='340' side='right' caption='[[4gzn]], [[Resolution|resolution]] 0.99Å' scene=''> | + | <StructureSection load='4gzn' size='340' side='right'caption='[[4gzn]], [[Resolution|resolution]] 0.99Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
- | <table><tr><td colspan='2'>[[4gzn]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GZN OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4GZN FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4gzn]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4GZN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4GZN FirstGlance]. <br> |
- | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </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=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4gzn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gzn OCA], [https://pdbe.org/4gzn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4gzn RCSB], [https://www.ebi.ac.uk/pdbsum/4gzn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4gzn ProSAT]</span></td></tr> |
- | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Zfp57 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>
| + | |
- | <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=4gzn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gzn OCA], [http://pdbe.org/4gzn PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4gzn RCSB], [http://www.ebi.ac.uk/pdbsum/4gzn PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4gzn ProSAT]</span></td></tr> | + | |
| </table> | | </table> |
| == Function == | | == Function == |
- | [[http://www.uniprot.org/uniprot/ZFP57_MOUSE ZFP57_MOUSE]] Transcription regulator required to maintain maternal and paternal gene imprinting, a process by which gene expression is restricted in a parent of origin-specific manner by epigenetic modification of genomic DNA and chromatin, including DNA methylation. Acts by controlling DNA methylation during the earliest multicellular stages of development at multiple imprinting control regions. Required for the establishment of maternal methylation imprints at SNRPN locus. Acts as a transcriptional repressor in Schwann cells. Binds to a 5'-TGCCGC-3' consensus sequence and recognizes the methylated CpG within this element.<ref>PMID:15070898</ref> <ref>PMID:18854139</ref> <ref>PMID:23059534</ref> | + | [https://www.uniprot.org/uniprot/ZFP57_MOUSE ZFP57_MOUSE] Transcription regulator required to maintain maternal and paternal gene imprinting, a process by which gene expression is restricted in a parent of origin-specific manner by epigenetic modification of genomic DNA and chromatin, including DNA methylation. Acts by controlling DNA methylation during the earliest multicellular stages of development at multiple imprinting control regions. Required for the establishment of maternal methylation imprints at SNRPN locus. Acts as a transcriptional repressor in Schwann cells. Binds to a 5'-TGCCGC-3' consensus sequence and recognizes the methylated CpG within this element.<ref>PMID:15070898</ref> <ref>PMID:18854139</ref> <ref>PMID:23059534</ref> |
| <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
- | [[Category: Lk3 transgenic mice]] | + | [[Category: Large Structures]] |
- | [[Category: Cheng, X]] | + | [[Category: Mus musculus]] |
- | [[Category: Liu, Y]] | + | [[Category: Cheng X]] |
- | [[Category: Zhang, X]]
| + | [[Category: Liu Y]] |
- | [[Category: Transcription-dna complex]] | + | [[Category: Zhang X]] |
- | [[Category: Zinc finger]] | + | |
| Structural highlights
Function
ZFP57_MOUSE Transcription regulator required to maintain maternal and paternal gene imprinting, a process by which gene expression is restricted in a parent of origin-specific manner by epigenetic modification of genomic DNA and chromatin, including DNA methylation. Acts by controlling DNA methylation during the earliest multicellular stages of development at multiple imprinting control regions. Required for the establishment of maternal methylation imprints at SNRPN locus. Acts as a transcriptional repressor in Schwann cells. Binds to a 5'-TGCCGC-3' consensus sequence and recognizes the methylated CpG within this element.[1] [2] [3]
Publication Abstract from PubMed
Zinc finger transcription factor Zfp57 recognizes the methylated CpG within the TGCCGC element. We determined the structure of the DNA-binding domain of Zfp57, consisting of two adjacent zinc fingers, in complex with fully methylated DNA at 1.0 A resolution. The first zinc finger contacts the 5' half (TGC), and the second recognizes the 3' half (CGC) of the recognition sequence. Zfp57 recognizes the two 5-methylcytosines (5mCs) asymmetrically: One involves hydrophobic interactions with Arg178, which also interacts with the neighboring 3' guanine and forms a 5mC-Arg-G interaction, while the other involves a layer of ordered water molecules. Two point mutations in patients with transient neonatal diabetes abolish DNA-binding activity. Zfp57 has reduced binding affinity for unmodified DNA and the oxidative products of 5mC.
An atomic model of Zfp57 recognition of CpG methylation within a specific DNA sequence.,Liu Y, Toh H, Sasaki H, Zhang X, Cheng X Genes Dev. 2012 Nov 1;26(21):2374-9. doi: 10.1101/gad.202200.112. Epub 2012 Oct, 11. PMID:23059534[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Alonso MB, Zoidl G, Taveggia C, Bosse F, Zoidl C, Rahman M, Parmantier E, Dean CH, Harris BS, Wrabetz L, Muller HW, Jessen KR, Mirsky R. Identification and characterization of ZFP-57, a novel zinc finger transcription factor in the mammalian peripheral nervous system. J Biol Chem. 2004 Jun 11;279(24):25653-64. Epub 2004 Apr 7. PMID:15070898 doi:http://dx.doi.org/10.1074/jbc.M400415200
- ↑ Li X, Ito M, Zhou F, Youngson N, Zuo X, Leder P, Ferguson-Smith AC. A maternal-zygotic effect gene, Zfp57, maintains both maternal and paternal imprints. Dev Cell. 2008 Oct;15(4):547-57. doi: 10.1016/j.devcel.2008.08.014. PMID:18854139 doi:http://dx.doi.org/10.1016/j.devcel.2008.08.014
- ↑ Liu Y, Toh H, Sasaki H, Zhang X, Cheng X. An atomic model of Zfp57 recognition of CpG methylation within a specific DNA sequence. Genes Dev. 2012 Nov 1;26(21):2374-9. doi: 10.1101/gad.202200.112. Epub 2012 Oct, 11. PMID:23059534 doi:http://dx.doi.org/10.1101/gad.202200.112
- ↑ Liu Y, Toh H, Sasaki H, Zhang X, Cheng X. An atomic model of Zfp57 recognition of CpG methylation within a specific DNA sequence. Genes Dev. 2012 Nov 1;26(21):2374-9. doi: 10.1101/gad.202200.112. Epub 2012 Oct, 11. PMID:23059534 doi:http://dx.doi.org/10.1101/gad.202200.112
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