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| | ==HOXB13-MEIS1 heterodimer bound to methylated DNA== | | ==HOXB13-MEIS1 heterodimer bound to methylated DNA== |
| - | <StructureSection load='5ego' size='340' side='right' caption='[[5ego]], [[Resolution|resolution]] 2.54Å' scene=''> | + | <StructureSection load='5ego' size='340' side='right'caption='[[5ego]], [[Resolution|resolution]] 2.54Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5ego]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EGO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5EGO FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5ego]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5EGO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5EGO 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]] 2.54Å</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=5ego FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ego OCA], [http://pdbe.org/5ego PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ego RCSB], [http://www.ebi.ac.uk/pdbsum/5ego PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ego 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=5ego FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ego OCA], [https://pdbe.org/5ego PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ego RCSB], [https://www.ebi.ac.uk/pdbsum/5ego PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ego ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/MEIS1_HUMAN MEIS1_HUMAN]] Disease susceptibility may be associated with variations affecting the gene represented in this entry. | + | [https://www.uniprot.org/uniprot/MEIS1_HUMAN MEIS1_HUMAN] Disease susceptibility may be associated with variations affecting the gene represented in this entry. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/HXB13_HUMAN HXB13_HUMAN]] Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis. [[http://www.uniprot.org/uniprot/MEIS1_HUMAN MEIS1_HUMAN]] Acts as a transcriptional regulator of PAX6. Acts as a transcriptional activator of PF4 in complex with PBX1 or PBX2. Required for hematopoiesis, megakaryocyte lineage development and vascular patterning. May function as a cofactor for HOXA7 and HOXA9 in the induction of myeloid leukemias.<ref>PMID:12609849</ref> | + | [https://www.uniprot.org/uniprot/MEIS1_HUMAN MEIS1_HUMAN] Acts as a transcriptional regulator of PAX6. Acts as a transcriptional activator of PF4 in complex with PBX1 or PBX2. Required for hematopoiesis, megakaryocyte lineage development and vascular patterning. May function as a cofactor for HOXA7 and HOXA9 in the induction of myeloid leukemias.<ref>PMID:12609849</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 5ego" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5ego" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Hox protein|Hox protein]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Jolma, A]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Morgunova, E]] | + | [[Category: Large Structures]] |
| - | [[Category: Popov, A]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Taipale, J]] | + | [[Category: Jolma A]] |
| - | [[Category: Yin, Y]] | + | [[Category: Morgunova E]] |
| - | [[Category: Bound to dna]] | + | [[Category: Popov A]] |
| - | [[Category: Complex]] | + | [[Category: Taipale J]] |
| - | [[Category: Heterodimer]] | + | [[Category: Yin Y]] |
| - | [[Category: Transcription]]
| + | |
| - | [[Category: Transcription factor]]
| + | |
| Structural highlights
Disease
MEIS1_HUMAN Disease susceptibility may be associated with variations affecting the gene represented in this entry.
Function
MEIS1_HUMAN Acts as a transcriptional regulator of PAX6. Acts as a transcriptional activator of PF4 in complex with PBX1 or PBX2. Required for hematopoiesis, megakaryocyte lineage development and vascular patterning. May function as a cofactor for HOXA7 and HOXA9 in the induction of myeloid leukemias.[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.
See Also
References
- ↑ Okada Y, Nagai R, Sato T, Matsuura E, Minami T, Morita I, Doi T. Homeodomain proteins MEIS1 and PBXs regulate the lineage-specific transcription of the platelet factor 4 gene. Blood. 2003 Jun 15;101(12):4748-56. Epub 2003 Feb 27. PMID:12609849 doi:10.1182/blood-2002-02-0380
- ↑ 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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