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| | ==Heterodimeric complex of transcription factors MEIS1 and DLX3 on specific DNA== | | ==Heterodimeric complex of transcription factors MEIS1 and DLX3 on specific DNA== |
| - | <StructureSection load='4xrs' size='340' side='right' caption='[[4xrs]], [[Resolution|resolution]] 3.50Å' scene=''> | + | <StructureSection load='4xrs' size='340' side='right'caption='[[4xrs]], [[Resolution|resolution]] 3.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4xrs]] is a 8 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4XRS OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4XRS FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4xrs]] is a 8 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=4XRS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4XRS FirstGlance]. <br> |
| - | </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=4xrs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xrs OCA], [http://pdbe.org/4xrs PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4xrs RCSB], [http://www.ebi.ac.uk/pdbsum/4xrs PDBsum]</span></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]] 3.5Å</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=4xrs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4xrs OCA], [https://pdbe.org/4xrs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4xrs RCSB], [https://www.ebi.ac.uk/pdbsum/4xrs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4xrs ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/DLX3_HUMAN DLX3_HUMAN]] Tricho-dento-osseous syndrome;Hypomaturation-hypoplastic amelogenesis imperfecta with taurodontism. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. [[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/DLX3_HUMAN DLX3_HUMAN]] Likely to play a regulatory role in the development of the ventral forebrain. May play a role in craniofacial patterning and morphogenesis. [[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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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Dave, K]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Enge, M]] | + | [[Category: Large Structures]] |
| - | [[Category: Jorma, A]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Kivioja, T]] | + | [[Category: Dave K]] |
| - | [[Category: Morgunova, E]] | + | [[Category: Enge M]] |
| - | [[Category: Nitta, K R]] | + | [[Category: Jorma A]] |
| - | [[Category: Popov, A]] | + | [[Category: Kivioja T]] |
| - | [[Category: Taipale, J]] | + | [[Category: Morgunova E]] |
| - | [[Category: Yin, Y]] | + | [[Category: Nitta KR]] |
| - | [[Category: Dna]] | + | [[Category: Popov A]] |
| - | [[Category: Heterodimer]] | + | [[Category: Taipale J]] |
| - | [[Category: Transcription]] | + | [[Category: Yin Y]] |
| 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
Gene expression is regulated by transcription factors (TFs), proteins that recognize short DNA sequence motifs. Such sequences are very common in the human genome, and an important determinant of the specificity of gene expression is the cooperative binding of multiple TFs to closely located motifs. However, interactions between DNA-bound TFs have not been systematically characterized. To identify TF pairs that bind cooperatively to DNA, and to characterize their spacing and orientation preferences, we have performed consecutive affinity-purification systematic evolution of ligands by exponential enrichment (CAP-SELEX) analysis of 9,400 TF-TF-DNA interactions. This analysis revealed 315 TF-TF interactions recognizing 618 heterodimeric motifs, most of which have not been previously described. The observed cooperativity occurred promiscuously between TFs from diverse structural families. Structural analysis of the TF pairs, including a novel crystal structure of MEIS1 and DLX3 bound to their identified recognition site, revealed that the interactions between the TFs were predominantly mediated by DNA. Most TF pair sites identified involved a large overlap between individual TF recognition motifs, and resulted in recognition of composite sites that were markedly different from the individual TF's motifs. Together, our results indicate that the DNA molecule commonly plays an active role in cooperative interactions that define the gene regulatory lexicon.
DNA-dependent formation of transcription factor pairs alters their binding specificity.,Jolma A, Yin Y, Nitta KR, Dave K, Popov A, Taipale M, Enge M, Kivioja T, Morgunova E, Taipale J Nature. 2015 Nov 19;527(7578):384-8. doi: 10.1038/nature15518. Epub 2015 Nov 9. PMID:26550823[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
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
- ↑ Jolma A, Yin Y, Nitta KR, Dave K, Popov A, Taipale M, Enge M, Kivioja T, Morgunova E, Taipale J. DNA-dependent formation of transcription factor pairs alters their binding specificity. Nature. 2015 Nov 19;527(7578):384-8. doi: 10.1038/nature15518. Epub 2015 Nov 9. PMID:26550823 doi:http://dx.doi.org/10.1038/nature15518
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