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| | ==Homeobox transcription factor CDX1 bound to methylated DNA== | | ==Homeobox transcription factor CDX1 bound to methylated DNA== |
| - | <StructureSection load='5lux' size='340' side='right' caption='[[5lux]], [[Resolution|resolution]] 3.23Å' scene=''> | + | <StructureSection load='5lux' size='340' side='right'caption='[[5lux]], [[Resolution|resolution]] 3.23Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5lux]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5LUX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5LUX FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5lux]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5LUX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5LUX FirstGlance]. <br> |
| - | </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> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.23Å</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=5lux FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lux OCA], [http://pdbe.org/5lux PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5lux RCSB], [http://www.ebi.ac.uk/pdbsum/5lux PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5lux ProSAT]</span></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></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=5lux FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lux OCA], [https://pdbe.org/5lux PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5lux RCSB], [https://www.ebi.ac.uk/pdbsum/5lux PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5lux ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CDX1_HUMAN CDX1_HUMAN]] Plays a role in transcriptional regulation (PubMed:24623306). Involved in activated KRAS-mediated transcriptional activation of PRKD1 in colorectal cancer (CRC) cells (PubMed:24623306). Binds to the PRKD1 promoter in colorectal cancer (CRC) cells (PubMed:24623306). Could play a role in the terminal differentiation of the intestine.<ref>PMID:24623306</ref> | + | [https://www.uniprot.org/uniprot/CDX1_HUMAN CDX1_HUMAN] Plays a role in transcriptional regulation (PubMed:24623306). Involved in activated KRAS-mediated transcriptional activation of PRKD1 in colorectal cancer (CRC) cells (PubMed:24623306). Binds to the PRKD1 promoter in colorectal cancer (CRC) cells (PubMed:24623306). Could play a role in the terminal differentiation of the intestine.<ref>PMID:24623306</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: Morgunova, E]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Popov, A]] | + | [[Category: Large Structures]] |
| - | [[Category: Taipale, J]] | + | [[Category: Morgunova E]] |
| - | [[Category: Methylated dna]] | + | [[Category: Popov A]] |
| - | [[Category: Transcription]] | + | [[Category: Taipale J]] |
| - | [[Category: Transcription factor]]
| + | |
| Structural highlights
Function
CDX1_HUMAN Plays a role in transcriptional regulation (PubMed:24623306). Involved in activated KRAS-mediated transcriptional activation of PRKD1 in colorectal cancer (CRC) cells (PubMed:24623306). Binds to the PRKD1 promoter in colorectal cancer (CRC) cells (PubMed:24623306). Could play a role in the terminal differentiation of the intestine.[1]
Publication Abstract from PubMed
The majority of CpG dinucleotides in the human genome are methylated at cytosine bases. However, active gene regulatory elements are generally hypomethylated relative to their flanking regions, and the binding of some transcription factors (TFs) is diminished by methylation of their target sequences. By analysis of 542 human TFs with methylation-sensitive SELEX (systematic evolution of ligands by exponential enrichment), we found that there are also many TFs that prefer CpG-methylated sequences. Most of these are in the extended homeodomain family. Structural analysis showed that homeodomain specificity for methylcytosine depends on direct hydrophobic interactions with the methylcytosine 5-methyl group. This study provides a systematic examination of the effect of an epigenetic DNA modification on human TF binding specificity and reveals that many developmentally important proteins display preference for mCpG-containing sequences.
Impact of cytosine methylation on DNA binding specificities of human transcription factors.,Yin Y, Morgunova E, Jolma A, Kaasinen E, Sahu B, Khund-Sayeed S, Das PK, Kivioja T, Dave K, Zhong F, Nitta KR, Taipale M, Popov A, Ginno PA, Domcke S, Yan J, Schubeler D, Vinson C, Taipale J Science. 2017 May 5;356(6337). pii: eaaj2239. doi: 10.1126/science.aaj2239. PMID:28473536[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Serra RW, Fang M, Park SM, Hutchinson L, Green MR. A KRAS-directed transcriptional silencing pathway that mediates the CpG island methylator phenotype. Elife. 2014 Mar 12;3:e02313. doi: 10.7554/eLife.02313. PMID:24623306 doi:http://dx.doi.org/10.7554/eLife.02313
- ↑ Yin Y, Morgunova E, Jolma A, Kaasinen E, Sahu B, Khund-Sayeed S, Das PK, Kivioja T, Dave K, Zhong F, Nitta KR, Taipale M, Popov A, Ginno PA, Domcke S, Yan J, Schubeler D, Vinson C, Taipale J. Impact of cytosine methylation on DNA binding specificities of human transcription factors. Science. 2017 May 5;356(6337). pii: eaaj2239. doi: 10.1126/science.aaj2239. PMID:28473536 doi:http://dx.doi.org/10.1126/science.aaj2239
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