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PMID: 10523646 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

PBX and MEIS as non-DNA-binding partners in trimeric complexes with HOX proteins.

Molecular and cellular biology ·Vol. 19 ·No. 11 ·1999-11-00 ·Pages 7577-88

Shanmugam K, Green NC, Rambaldi I, Saragovi HU, Featherstone MS

Abstract

HOX, PBX, and MEIS transcription factors bind DNA through a homeodomain. PBX proteins bind DNA cooperatively as heterodimers with MEIS family members and also with HOX proteins from paralog groups 1 to 10. MEIS proteins cooperatively bind DNA with ABD-B class HOX proteins of groups 9 and 10. Here, we examine aspects of dimeric and higher-order interactions between these three homeodomain classes. The most significant results can be summarized as follows. (i) Most of PBX N terminal to the homeodomain is required for efficient cooperative binding with HOXD4 and HOXD9. (ii) MEIS and PBX proteins form higher-order complexes on a heterodimeric binding site. (iii) Although MEIS does not cooperatively bind DNA with ANTP class HOX proteins, it does form a trimer as a non-DNA-binding partner with DNA-bound PBX-HOXD4. (iv) The N terminus of HOXD4 negatively regulates trimer formation. (v) MEIS forms a similar trimer with DNA-bound PBX-HOXD9. (vi) A related trimer (where MEIS is a non-DNA-binding partner) is formed on a transcriptional promoter within the cell. (vii) We observe an additional trimer class involving non-DNA-bound PBX and DNA-bound MEIS-HOXD9 or MEIS-HOXD10 heterodimers that is enhanced by mutation of the PBX homeodomain. (viii) In this latter trimer, PBX is likely to contact both MEIS and HOXD9/D10. (ix) The stability of DNA binding by all trimers is enhanced relative to the heterodimers. These findings suggest novel functions for PBX and MEIS in modulating the function of DNA-bound MEIS-HOX and PBX-HOX heterodimers, respectively.

MeSH Terms
Antennapedia Homeodomain Protein Binding Sites DNA-Binding Proteins/metabolism Dimerization Homeodomain Proteins/classification,metabolism Macromolecular Substances Models, Genetic Multigene Family Myeloid Ecotropic Viral Integration Site 1 Protein Neoplasm Proteins/metabolism Nuclear Proteins Pre-B-Cell Leukemia Transcription Factor 1 Protein Binding Protein Structure, Quaternary Proto-Oncogene Proteins/metabolism Transcription Factors/classification,metabolism
Chemicals
Antennapedia Homeodomain Protein DNA-Binding Proteins Homeodomain Proteins Macromolecular Substances Myeloid Ecotropic Viral Integration Site 1 Protein Neoplasm Proteins Nuclear Proteins Pre-B-Cell Leukemia Transcription Factor 1 Proto-Oncogene Proteins Transcription Factors pbx1 protein, human
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Shanmugam K
McGill Cancer Centre, McGill University, Montreal, Quebec, Canada H3G 1Y6.
Green N C
Rambaldi I
Saragovi H U
Featherstone M S
References (63)
63 references, click to expand
  1. An autoregulatory enhancer element of the Drosophila homeotic gene Deformed.
    EMBO J. 1990 Dec;9(13):4287-97 PMID: 1979945
  2. The Hox cooperativity motif of the chimeric oncoprotein E2a-Pbx1 is necessary and sufficient for oncogenesis.
    Mol Cell Biol. 1997 Jan;17(1):81-8 PMID: 8972188
  3. Crystal structure of a MAT alpha 2 homeodomain-operator complex suggests a general model for homeodomain-DNA interactions.
    Cell. 1991 Nov 1;67(3):517-28 PMID: 1682054
  4. PBX2 and PBX3, new homeobox genes with extensive homology to the human proto-oncogene PBX1.
    Mol Cell Biol. 1991 Dec;11(12):6149-57 PMID: 1682799
  5. Homeobox genes and axial patterning.
    Cell. 1992 Jan 24;68(2):283-302 PMID: 1346368
  6. An autoregulatory element of the murine Hox-4.2 gene.
    EMBO J. 1992 Oct;11(10):3673-80 PMID: 1356763
  7. New motif in PBX genes.
    Nat Genet. 1992 Aug;1(5):319-20 PMID: 1363814
  8. extradenticle, a regulator of homeotic gene activity, is a homolog of the homeobox-containing human proto-oncogene pbx1.
    Cell. 1993 Sep 24;74(6):1101-12 PMID: 8104703
  9. Determination of the nuclear magnetic resonance solution structure of an Antennapedia homeodomain-DNA complex.
    J Mol Biol. 1993 Dec 20;234(4):1084-93 PMID: 7903398
  10. Developmental functions of mammalian Hox genes.
    Mol Hum Reprod. 1997 Feb;3(2):115-31 PMID: 9239717
  11. Cross-regulation in the mouse HoxB complex: the expression of Hoxb2 in rhombomere 4 is regulated by Hoxb1.
    Genes Dev. 1997 Jul 15;11(14):1885-95 PMID: 9242495
  12. Meis proteins are major in vivo DNA binding partners for wild-type but not chimeric Pbx proteins.
    Mol Cell Biol. 1997 Oct;17(10):5679-87 PMID: 9315626
  13. Analysis of TALE superclass homeobox genes (MEIS, PBC, KNOX, Iroquois, TGIF) reveals a novel domain conserved between plants and animals.
    Nucleic Acids Res. 1997 Nov 1;25(21):4173-80 PMID: 9336443
  14. AbdB-like Hox proteins stabilize DNA binding by the Meis1 homeodomain proteins.
    Mol Cell Biol. 1997 Nov;17(11):6448-58 PMID: 9343407
  15. Nuclear translocation of extradenticle requires homothorax, which encodes an extradenticle-related homeodomain protein.
    Cell. 1997 Oct 17;91(2):171-83 PMID: 9346235
  16. Meis1 and pKnox1 bind DNA cooperatively with Pbx1 utilizing an interaction surface disrupted in oncoprotein E2a-Pbx1.
    Proc Natl Acad Sci U S A. 1997 Dec 23;94(26):14553-8 PMID: 9405651
  17. Prep1, a novel functional partner of Pbx proteins.
    EMBO J. 1998 Mar 2;17(5):1423-33 PMID: 9482739
  18. The novel homeoprotein Prep1 modulates Pbx-Hox protein cooperativity.
    EMBO J. 1998 Mar 2;17(5):1434-45 PMID: 9482740
  19. A conserved C-terminal domain in PBX increases DNA binding by the PBX homeodomain and is not a primary site of contact for the YPWM motif of HOXA1.
    J Biol Chem. 1998 May 22;273(21):13273-9 PMID: 9582372
  20. Hoxa9 transforms primary bone marrow cells through specific collaboration with Meis1a but not Pbx1b.
    EMBO J. 1998 Jul 1;17(13):3714-25 PMID: 9649441
  21. An endocrine-exocrine switch in the activity of the pancreatic homeodomain protein PDX1 through formation of a trimeric complex with PBX1b and MRG1 (MEIS2).
    Mol Cell Biol. 1998 Sep;18(9):5109-20 PMID: 9710595
  22. Definition of the transcriptional activation domains of three human HOX proteins depends on the DNA-binding context.
    Mol Cell Biol. 1998 Nov;18(11):6201-12 PMID: 9774637
  23. Structure of a HoxB1-Pbx1 heterodimer bound to DNA: role of the hexapeptide and a fourth homeodomain helix in complex formation.
    Cell. 1999 Feb 19;96(4):587-97 PMID: 10052460
  24. Structure of a DNA-bound Ultrabithorax-Extradenticle homeodomain complex.
    Nature. 1999 Feb 25;397(6721):714-9 PMID: 10067897
  25. HOXA9 forms triple complexes with PBX2 and MEIS1 in myeloid cells.
    Mol Cell Biol. 1999 Apr;19(4):3051-61 PMID: 10082572
  26. Control of the nuclear localization of Extradenticle by competing nuclear import and export signals.
    Genes Dev. 1999 Apr 15;13(8):935-45 PMID: 10215621
  27. The subcellular localization of PBX1 and EXD proteins depends on nuclear import and export signals and is modulated by association with PREP1 and HTH.
    Genes Dev. 1999 Apr 15;13(8):946-53 PMID: 10215622
  28. Chromosomal translocation t(1;19) results in synthesis of a homeobox fusion mRNA that codes for a potential chimeric transcription factor.
    Cell. 1990 Feb 23;60(4):535-45 PMID: 1967982
  29. A new homeobox gene contributes the DNA binding domain of the t(1;19) translocation protein in pre-B ALL.
    Cell. 1990 Feb 23;60(4):547-55 PMID: 1967983
  30. Crystal structure of an engrailed homeodomain-DNA complex at 2.8 A resolution: a framework for understanding homeodomain-DNA interactions.
    Cell. 1990 Nov 2;63(3):579-90 PMID: 1977522
  31. Molecular cloning and expression of a hexameric Drosophila heat shock factor subject to negative regulation.
    Cell. 1990 Nov 30;63(5):1085-97 PMID: 2257625
  32. A proline-rich transcriptional activation domain in murine HOXD-4 (HOX-4.2).
    Nucleic Acids Res. 1994 Feb 11;22(3):376-82 PMID: 7907418
  33. Deformed protein binding sites and cofactor binding sites are required for the function of a small segment-specific regulatory element in Drosophila embryos.
    EMBO J. 1994 May 15;13(10):2362-77 PMID: 7910795
  34. Hox genes in vertebrate development.
    Cell. 1994 Jul 29;78(2):191-201 PMID: 7913880
  35. Homeodomain-DNA recognition.
    Cell. 1994 Jul 29;78(2):211-23 PMID: 8044836
  36. Extradenticle protein is a selective cofactor for the Drosophila homeotics: role of the homeodomain and YPWM amino acid motif in the interaction.
    Proc Natl Acad Sci U S A. 1995 Jan 31;92(3):739-43 PMID: 7846045
  37. A homeo domain protein lacking specific side chains of helix 3 can still bind DNA and direct transcriptional repression.
    Genes Dev. 1995 Jan 15;9(2):182-92 PMID: 7851792
  38. Pbx proteins display hexapeptide-dependent cooperative DNA binding with a subset of Hox proteins.
    Genes Dev. 1995 Mar 15;9(6):663-74 PMID: 7729685
  39. Both Pbx1 and E2A-Pbx1 bind the DNA motif ATCAATCAA cooperatively with the products of multiple murine Hox genes, some of which are themselves oncogenes.
    Mol Cell Biol. 1995 Jul;15(7):3786-95 PMID: 7791786
  40. Segmental expression of Hoxb-1 is controlled by a highly conserved autoregulatory loop dependent upon exd/pbx.
    Cell. 1995 Jun 30;81(7):1031-42 PMID: 7600572
  41. Cooperative interactions between HOX and PBX proteins mediated by a conserved peptide motif.
    Mol Cell Biol. 1995 Aug;15(8):3989-97 PMID: 7623795
  42. Meis1, a PBX1-related homeobox gene involved in myeloid leukemia in BXH-2 mice.
    Mol Cell Biol. 1995 Oct;15(10):5434-43 PMID: 7565694
  43. The pentapeptide motif of Hox proteins is required for cooperative DNA binding with Pbx1, physically contacts Pbx1, and enhances DNA binding by Pbx1.
    Mol Cell Biol. 1995 Oct;15(10):5811-9 PMID: 7565734
  44. The hexapeptide LFPWMR in Hoxb-8 is required for cooperative DNA binding with Pbx1 and Pbx2 proteins.
    Proc Natl Acad Sci U S A. 1995 Sep 26;92(20):9166-70 PMID: 7568094
  45. Selective repression of transcriptional activators by Pbx1 does not require the homeodomain.
    Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):470-4 PMID: 8552663
  46. Cooperative activation of Hoxa and Pbx1-related genes in murine myeloid leukaemias.
    Nat Genet. 1996 Feb;12(2):149-53 PMID: 8563752
  47. Specific residues in the Pbx homeodomain differentially modulate the DNA-binding activity of Hox and Engrailed proteins.
    Development. 1997 Mar;124(5):1089-98 PMID: 9056783
  48. The Abd-B-like Hox homeodomain proteins can be subdivided by the ability to form complexes with Pbx1a on a novel DNA target.
    J Biol Chem. 1997 Mar 28;272(13):8198-206 PMID: 9079637
  49. Distinct HOX N-terminal arm residues are responsible for specificity of DNA recognition by HOX monomers and HOX.PBX heterodimers.
    J Biol Chem. 1997 Mar 28;272(13):8635-43 PMID: 9079695
  50. Positive cross-regulation and enhancer sharing: two mechanisms for specifying overlapping Hox expression patterns.
    Genes Dev. 1997 Apr 1;11(7):900-13 PMID: 9106661
  51. A model for extradenticle function as a switch that changes HOX proteins from repressors to activators.
    EMBO J. 1997 Apr 15;16(8):2032-42 PMID: 9155029
  52. Switching the in vivo specificity of a minimal Hox-responsive element.
    Development. 1997 May;124(10):2007-14 PMID: 9169847
  53. Functional dissection of a transcriptionally active, target-specific Hox-Pbx complex.
    EMBO J. 1997 Jun 16;16(12):3644-54 PMID: 9218805
  54. High-affinity binding sites for the Deformed protein are required for the function of an autoregulatory enhancer of the Deformed gene.
    Genes Dev. 1991 Feb;5(2):278-86 PMID: 1995417
  55. Hox homeodomain proteins exhibit selective complex stabilities with Pbx and DNA.
    Nucleic Acids Res. 1996 Mar 1;24(5):898-906 PMID: 8600458
  56. Repression by HoxA7 is mediated by the homeodomain and the modulatory action of its N-terminal-arm residues.
    Mol Cell Biol. 1996 Jun;16(6):2678-88 PMID: 8649375
  57. A structural model for a homeotic protein-extradenticle-DNA complex accounts for the choice of HOX protein in the heterodimer.
    Proc Natl Acad Sci U S A. 1996 May 28;93(11):5223-8 PMID: 8643557
  58. Structural determinants within Pbx1 that mediate cooperative DNA binding with pentapeptide-containing Hox proteins: proposal for a model of a Pbx1-Hox-DNA complex.
    Mol Cell Biol. 1996 Apr;16(4):1632-40 PMID: 8657138
  59. Pbx modulation of Hox homeodomain amino-terminal arms establishes different DNA-binding specificities across the Hox locus.
    Mol Cell Biol. 1996 Apr;16(4):1734-45 PMID: 8657149
  60. Hydration and DNA recognition by homeodomains.
    Cell. 1996 Jun 28;85(7):1057-65 PMID: 8674112
  61. Extra specificity from extradenticle: the partnership between HOX and PBX/EXD homeodomain proteins.
    Trends Genet. 1996 Jul;12(7):258-62 PMID: 8763497
  62. HMG1 interacts with HOX proteins and enhances their DNA binding and transcriptional activation.
    EMBO J. 1996 Sep 16;15(18):4981-91 PMID: 8890171
  63. Residues flanking the HOX YPWM motif contribute to cooperative interactions with PBX.
    J Biol Chem. 1997 Jul 25;272(30):19081-7 PMID: 9228093
Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.19.11.7577
Published
1999-11-00
Pages
7577-88
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC84774
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.19.11.7577 PMC Full Text View journal details
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