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Hox Genes pp 3-16 | Cite as

Regulation of Hox Activity: Insights from Protein Motifs

  • Samir Merabet
  • Nagraj Sambrani
  • Jacques Pradel
  • Yacine Graba
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 689)

Abstract

Deciphering the molecular bases of animal body plan construction is a central question in developmental and evolutionary biology. Genome analyses of a number of metazoans indicate that widely conserved regulatory molecules underlie the amazing diversity of animal body plans, suggesting that these molecules are reiteratively used for multiple purposes. Hox proteins constitute a good example of such molecules and provide the framework to address the mechanisms underlying transcriptional specificity and diversity in development and evolution. Here we examine the current knowledge of the molecular bases of Hox-mediated transcriptional control, focusing on how this control is encoded within protein sequences and structures. The survey suggests that the homeodomain is part of an extended multifunctional unit coordinating DNA binding and activity regulation and highlights the need for further advances in our understanding of Hox protein activity.

Keywords

Repression Domain Paralog Group Recognition Helix Animal Body Plan Antennapedia Homeodomain 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    McGinnis W, Krumlauf R. Homeobox genes and axial patterning. Cell 1992; 68:283–302.PubMedCrossRefGoogle Scholar
  2. 2.
    Gellon G, McGinnis W. Shaping animal body plans in development and evolution by modulation of Hox expression patterns. Bioessays 1998; 20:116–25.PubMedCrossRefGoogle Scholar
  3. 3.
    Deutsch JS, Mouchel-Vielh E. Hox genes and the crustacean body plan. Bioessays 2003; 25:878–87.PubMedCrossRefGoogle Scholar
  4. 4.
    Duboule D. The rise and fall of Hox gene clusters. Development 2007; 134:2549–60.PubMedCrossRefGoogle Scholar
  5. 5.
    Warren R, Carroll S. Homeotic genes and diversification of the insect body plan. Curr Opin Genet Dev 1995; 5:459–465.PubMedCrossRefGoogle Scholar
  6. 6.
    Argiropoulos B, Humphries RK. Hox genes in hematopoiesis and leukemogenesis. Oncogene 2007; 26:6766–76.PubMedCrossRefGoogle Scholar
  7. 7.
    Eklund EA. The role of HOX genes in malignant myeloid disease. Curr Opin Hematol 2007; 14:85–9.PubMedCrossRefGoogle Scholar
  8. 8.
    Cillo C, Cantile M, Faiella A et al. Homeobox genes in normal and malignant cells. J Cell Physiol 2001; 188:161–9.PubMedCrossRefGoogle Scholar
  9. 9.
    Abate-Shen C. Deregulated homeobox gene expression in cancer: cause or consequence? Nat Rev Cancer 2002; 2:777–85.PubMedCrossRefGoogle Scholar
  10. 10.
    Hombria JC, Lovegrove B. Beyond homeosis—HOX function in morphogenesis and organogenesis. Differentiation 2003; 71:461–76.PubMedCrossRefGoogle Scholar
  11. 11.
    Pearson JC, Lemons D, McGinnis W. Modulating Hox gene functions during animal body patterning. Nat Rev Genet 2005; 6:893–904.PubMedCrossRefGoogle Scholar
  12. 12.
    Hueber SD, Lohmann I. Shaping segments: Hox gene function in the genomic age. Bioessays 2008; 30:965–79.PubMedCrossRefGoogle Scholar
  13. 13.
    Hueber SD, Bezdan D, Henz SR et al. Comparative analysis of Hox downstream genes in Drosophila. Development 2007; 134:381–92.PubMedCrossRefGoogle Scholar
  14. 14.
    Graba Y, Aragnol D, Pradel J. Drosophila Hox complex downstream targets and the function of homeotic genes. BioEssays 1997; 19:379–388.PubMedCrossRefGoogle Scholar
  15. 15.
    Gehring WJ, Qian YQ, Billeter M et al. Homeodomain-DNA recognition. Cell 1994; 78:211–223.PubMedCrossRefGoogle Scholar
  16. 16.
    Mann RS, Chan S-K. Extra specificity from extradenticle: The partnership between HOX and PBX/ EXD homeodomain proteins. Trends Genet 1996; 12:258–262.PubMedCrossRefGoogle Scholar
  17. 17.
    Mann RS, Hogness DS. Functional dissection of Ultrabithorax proteins in D. melanogaster. Cell 1990; 60:597–610.PubMedCrossRefGoogle Scholar
  18. 18.
    Chan S-K, Mann RS. The segment identity functions of Ultrabithorax are contained within its homeo domain and carboxy-terminal sequences. Genes Dev 1993; 7:796–811.PubMedCrossRefGoogle Scholar
  19. 19.
    Lin L, McGinnis W. Mapping functional specificity in the Dfd and Ubx homeo domains. Genes Dev 1992; 6:1071–1081.PubMedCrossRefGoogle Scholar
  20. 20.
    Zeng W, Andrew DJ, Mathies LD et al. Ectopic expression and function of the Antp and Scr homeotic genes: The N terminus of the homeodomain is critical to functional specificity. Development 1993; 118:339–352.PubMedGoogle Scholar
  21. 21.
    Furukubo-Tokunaga K, Flister S, Gehring WJ. Functional specificity of the Antennapedia homeodomain. Proc Natl Acad Sci Usa 1993; 90:6360–6364.PubMedCrossRefGoogle Scholar
  22. 22.
    Chauvet S, Merabet S, Bilder D et al. Distinct Hox protein sequences determine specificity in different tissues. Proc Natl Acad Sci USA 2000; 97:4064–9.PubMedCrossRefGoogle Scholar
  23. 23.
    Larroux C, Fahey B, Degnan SM, et al. The NK homeobox gene cluster predates the origin of Hox genes. Curr Biol 2007; 17:706–10.PubMedCrossRefGoogle Scholar
  24. 24.
    Peterson KJ, Sperling EA. Poriferan ANTP genes: primitively simple or secondarily reduced? Evol Dev 2007; 9:405–8.PubMedCrossRefGoogle Scholar
  25. 25.
    Jakob W, Schierwater B. Changing hydrozoan bauplans by silencing Hox-like genes. PLoS ONE 2007; 2:e694.PubMedCrossRefGoogle Scholar
  26. 26.
    Kamm K, Schierwater B, Jakob W et al. Axial patterning and diversification in the cnidaria predate the Hox system. Curr Biol 2006; 16:920–6.PubMedCrossRefGoogle Scholar
  27. 27.
    Chiori R, Jager M, Denker E et al. Are Hox genes ancestrally involved in axial patterning? Evidence from the hydrozoan Clytia hemisphaerica (Cnidaria). PLoS ONE 2009; 4:e4231.PubMedCrossRefGoogle Scholar
  28. 28.
    Balavoine G, de Rosa R, Adoutte A. Hox clusters and bilaterian phylogeny. Mol Phylogenet Evol 2002; 24:366–73.PubMedCrossRefGoogle Scholar
  29. 29.
    Feng JA, Johnson RC, Dickerson RE. Hin recombinase bound to DNA: the origin of specificity in major and minor groove interactions. Science 1994; 263:348–55.PubMedCrossRefGoogle Scholar
  30. 30.
    Deutsch J, Lopez P. Are transposition events at the origin of the bilaterian Hox complexes? Evolving pathways, Cambridge University Press, 2008;13.Google Scholar
  31. 31.
    Gehring WJ, Affolter M, Bürglin T. Homeodomain proteins. Annu Rev Biochem 1994; 63:487–526.PubMedCrossRefGoogle Scholar
  32. 32.
    Berger MF, Badis G, Gehrke AR et al. Variation in homeodomain DNA binding revealed by high-resolution analysis of sequence preferences. Cell 2008; 133:1266–76.PubMedCrossRefGoogle Scholar
  33. 33.
    Noyes MB, Christensen RG, Wakabayashi A et al. Analysis of homeodomain specificities allows the family-wide prediction of preferred recognition sites. Cell2008; 133:1277–89.PubMedCrossRefGoogle Scholar
  34. 34.
    Ekker SC et al. The degree of variation in DNA sequence recognition among four Drosophila homeotic proteins. EMBO J 1994; 13:3551–3560.PubMedGoogle Scholar
  35. 35.
    Mann RS. The specificity of homeotic gene function. BioEssays 1995; 17:855–863.PubMedCrossRefGoogle Scholar
  36. 36.
    Chan SK, Mann RS. The segment identity functions of Ultrabithorax are contained within its homeo domain and carboxy-terminal sequences. Genes Dev 1993; 7:796–811.PubMedCrossRefGoogle Scholar
  37. 37.
    LaRonde-LeBlanc NA, Wolberger C. Structure of HoxA9 and Pbx1 bound to DNA: Hox hexapeptide and DNA recognition anterior to posterior. Genes Dev 2003; 17:2060–72.PubMedCrossRefGoogle Scholar
  38. 38.
    Joshi R et al. Functional specificity of a Hox protein mediated by the recognition of minor groove structure. Cell 2007; 131:530–43.PubMedCrossRefGoogle Scholar
  39. 39.
    Frazee RW, Taylor JA, Tullius TD. Interchange of DNA-binding modes in the Deformed and Ultrabithorax homeodomains: a structural role for the N-terminal arm. J Mol Biol 2002; 323:665–83.PubMedCrossRefGoogle Scholar
  40. 40.
    Li X, McGinnis W. Activity regulation of Hox proteins, a mechanism for altering functional specificity in development and evolution. Proc Natl Acad Sci USA 1999; 96:6802–7.PubMedCrossRefGoogle Scholar
  41. 41.
    Li X, Murre C, McGinnis W. Activity regulation of a Hox protein and a role for the homeodomain in inhibiting transcriptional activation. Embo J 1999; 18:198–211.PubMedCrossRefGoogle Scholar
  42. 42.
    Suzuki M, Ueno N, Kuroiwa A. Hox proteins functionally cooperate with the GC box-binding protein system through distinct domains. J Biol Chem 2003; 278:30148–56.PubMedCrossRefGoogle Scholar
  43. 43.
    Zappavigna V, Sartori D, Mavilio F. Specificity of HOX protein function depends on DNA-protein and protein-protein interactions, both mediated by the homeo domain. Genes Dev 1994; 8:732–744.PubMedCrossRefGoogle Scholar
  44. 44.
    Schnabel CA, Abate-Shen C. Repression by HoxA7 is mediated by the homeodomain and the modulatory action of its N-terminal-arm residues. Mol Cell Biol 1996; 16:2678–2688.PubMedGoogle Scholar
  45. 45.
    Roth JJ, Breitenbach M, Wagner GP. Repressor domain and nuclear localization signal of the murine Hoxa-11 protein are located in the homeodomain: no evidence for role of poly alanine stretches in transcriptional repression. J Exp Zoolog B Mol Dev Evol 2005; 304:468–75.CrossRefGoogle Scholar
  46. 46.
    Chariot A, Gielen J, Merville MP et al. The homeodomain-containing proteins: an update on their interacting partners. Biochem Pharmacol 1999; 58:1851–7.PubMedCrossRefGoogle Scholar
  47. 47.
    Chariot A, van Lint C, Chapelier M et al. CBP and histone deacetylase inhibition enhance the transactivation potential of the HOXB7 homeodomain-containing protein. Oncogene 1999; 18:4007–14.PubMedCrossRefGoogle Scholar
  48. 48.
    Saleh M, Rambaldi I, Yang XJ et al. Cell signaling switches HOX-PBX complexes from repressors to activators of transcription mediated by histone deacetylases and histone acetyltransferases. Mol Cell Biol 2000; 20:8623–33.PubMedCrossRefGoogle Scholar
  49. 49.
    Shen W, Chrobak D, Krishnan K et al. HOXB6 protein is bound to CREB-binding protein and represses globin expression in a DNA binding-dependent, PBX interaction-independent process. J Biol Chem 2004; 279:39895–904.PubMedCrossRefGoogle Scholar
  50. 50.
    Shen WF, Krishnan K, Lawrence HJ et al. The Hox homeodomain proteins block CBP histone acetyltransferase activity. Mol Cell Biol 2001; 21:7509–22.PubMedCrossRefGoogle Scholar
  51. 51.
    Zhu AH, Kuziora MA. Functional domains in the Deformed protein. Development 1996; 122:1577–1587.PubMedGoogle Scholar
  52. 52.
    Zhu A, Kuziora MA. Homeodomain interaction with the beta subunit of the general transcription factor TFIIE. J Biol Chem 1996; 271:20993–6.PubMedCrossRefGoogle Scholar
  53. 53.
    Prevot D et al. The leukemia-associated protein Btg1 and the p53-regulated protein Btg2 interact with the homeoprotein Hoxb9 and enhance its transcriptional activation. J Biol Chem 2000; 275:147–53.PubMedCrossRefGoogle Scholar
  54. 54.
    Yang X et al decapentaplegic is a direct target of dTcf repression in the Drosophila visceral mesoderm. Development 2000; 127:3695–702.PubMedGoogle Scholar
  55. 55.
    Plaza S et al. Cross-regulatory protein-protein interactions between Hox and Pax transcription factors. Proc Natl Acad Sci USA 2008; 105:13439–44.PubMedCrossRefGoogle Scholar
  56. 56.
    Luo L, Yang X, Takihara Y et al. The cell-cycle regulator geminin inhibits Hox function through direct and Polycomb-mediated interactions. Nature 2004; 427:749–53.PubMedCrossRefGoogle Scholar
  57. 57.
    Kataoka K, Yoshitomo-Nakagawa K, Shioda S et al. A set of Hox proteins interact with the Maf oncoprotein to inhibit its DNA binding, transactivation and transforming activities. J Biol Chem 2001; 276:819–26.PubMedCrossRefGoogle Scholar
  58. 58.
    Kirito K, Fox N, Kaushansky K. Thrombopoietin induces HOXA9 nuclear transport in immature hematopoietic cells: potential mechanism by which the hormone favorably affects hematopoietic stem cells. Mol Cell Biol 2004; 24:6751–62.PubMedCrossRefGoogle Scholar
  59. 59.
    Joliot A, Pernelle C, Deagostini-Bazin H et al. Antennapedia homeobox peptide regulates neural morphogenesis. Proc Natl Acad Sci USA 1991; 88:1864–8.PubMedCrossRefGoogle Scholar
  60. 60.
    Perez F et al. Antennapedia homeobox as a signal for the cellular internalization and nuclear addressing of a small exogenous peptide. J Cell Sci 1992; 102(Pt 4):717–22.PubMedGoogle Scholar
  61. 61.
    Chatelin L, Volovitch M, Joliot AH et al. Transcription factor Hoxa-5 is taken up by cells in culture and conveyed to their nuclei. Mech Dev 1996; 55:111–7.PubMedCrossRefGoogle Scholar
  62. 62.
    Derossi D, Joliot AH, Chassaing G et al. The third helix of the Antennapedia homeodomain translocates through biological membranes. J Biol Chem 1994; 269:10444–50.PubMedGoogle Scholar
  63. 63.
    Sugiyama S, Di Nardo AA, Aizawa S et al. Experience-dependent transfer of Otx2 homeoprotein into the visual cortex activates postnatal plasticity. Cell 2008; 134:508–20.PubMedCrossRefGoogle Scholar
  64. 64.
    In der Rieden PM, Mainguy G, Woltering JM et al. Homeodomain to hexapeptide or PBC-interactiondomain distance: size apparently matters. Trends Genet 2004; 20:76–9.PubMedCrossRefGoogle Scholar
  65. 65.
    Piper DE, Batchelor AH, Chang CP et al. Structure of a HoxB1-Pbx1 heterodimer bound to DNA: role of the hexapeptide and a fourth homeodomain helix in complex formation. Cell 1999; 96:587–97.PubMedCrossRefGoogle Scholar
  66. 66.
    Bürglin TR. Analysis of TALE superclass homeobox genes (MEIS, PBC, KNOX, Iroquois, TGIF) reveals a novel domain conserved between plants and animals. Nucleic Acids Res 1997; 25:4173–4180.PubMedCrossRefGoogle Scholar
  67. 67.
    Mukherjee K, Burglin TR. Comprehensive analysis of animal TALE homeobox genes: new conserved motifs and cases of accelerated evolution. J Mol Evol 2007; 65:137–53.PubMedCrossRefGoogle Scholar
  68. 68.
    Peifer M, Wieschaus E. Mutations in the Drosophila gene extradenticle affect the way specific homeo domain proteins regulate segmental identity. Genes Dev 1990; 4:1209–23.PubMedCrossRefGoogle Scholar
  69. 69.
    Nourse J, Mellentin JD, Galili N et al. Chromosomal translocation t(1; 19) results in the synthesis of a homeobox fusion mRNA that codes for a potential chimeric transcription factor. Cell 1990; 60:535–545.PubMedCrossRefGoogle Scholar
  70. 70.
    Sanchez M, Jennings PA, Murre C. Conformational changes induced in Hoxb-8/Pbx-1 heterodimers in solution and upon interaction with specific DNA. Mol Cell Biol 1997; 17:5369–76.PubMedGoogle Scholar
  71. 71.
    Phelan ML, Rambaldi I, Featherstone MS. Cooperative interactions between HOX and PBX proteins mediated by a conserved peptide motif. Mol Cell Biol 1995; 15:3989–3997.PubMedGoogle Scholar
  72. 72.
    Knoepfler PS, Kamps MP. 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; 15:5811–5819.PubMedGoogle Scholar
  73. 73.
    Johnson FJ, Parker E, Krasnow MA. Extradenticle protein is a selective cofactor for the Drosophila homeotics: Role of the homeodomain and YPWM amino acid motif in the interaction. Proc Nat Acad Sci USA 1995; 92:739–743.PubMedCrossRefGoogle Scholar
  74. 74.
    Passner JM, Ryoo HD, Shen L et al. Structure of a DNA-bound Ultrabithorax-Extradenticle homeodomain complex. Nature 1999; 397:714–9.PubMedCrossRefGoogle Scholar
  75. 75.
    Chan S-K, Mann RS. A structural model for a homeotic protein-Extradenticle-DNA complex accounts for the choice of HOX protein in the heterodimer. Proc Natl Acad Sci USA 1996; 93:5223–5228.PubMedCrossRefGoogle Scholar
  76. 76.
    Shen WF, Chang CP, Rozenfeld S et al. Hox homeodomain proteins exhibit selective complex stabilities with Pbx and DNA. Nucleic Acids Res 1996; 24:898–906.PubMedCrossRefGoogle Scholar
  77. 77.
    Wilson DS, Sheng GJ, Jun S et al. Conservation and diversification in homeodomain-DNA interactions: A comparative genetic analysis. Proc Natl Acad Sci USA 1996; 93:6886–6891.PubMedCrossRefGoogle Scholar
  78. 78.
    Wilson DS, Desplan C. Structural basis of Hox specificity. Nat Struct Biol 1999; 6:297–300.PubMedCrossRefGoogle Scholar
  79. 79.
    Ryoo HD, Marty T, Casares F et al. Regulation of Hox target genes by a DNA bound Homothorax/ Hox/Extradenticle complex. Development 1999; 126:5137–48.PubMedGoogle Scholar
  80. 80.
    Ryoo HD, Mann RS. The control of trunk Hox specificity and activity by Extradenticle. Genes Dev 1999; 13:1704–16.PubMedCrossRefGoogle Scholar
  81. 81.
    Chan SK, Ryoo HD, Gould A et al. Switching the in vivo specificity of a minimal Hox-responsive element. Development 1997; 124:2007–2014.PubMedGoogle Scholar
  82. 82.
    Morgan R, In der Rieden P, Hooiveld MH et al. Identifying HOX paralog groups by the PBX-binding region. Trends Genet 2000; 16:66–7.PubMedCrossRefGoogle Scholar
  83. 83.
    Ebner A, Cabernard C, Affolter M et al. Recognition of distinct target sites by a unique Labial/Extradenticle/ Homothorax complex. Development 2005; 132:1591–600.PubMedCrossRefGoogle Scholar
  84. 84.
    Li-Kroeger D, Witt LM, Grimes HL et al. Hox and senseless antagonism functions as a molecular switch to regulate EGF secretion in the Drosophila PNS. Dev Cell 2008; 15:298–308.PubMedCrossRefGoogle Scholar
  85. 85.
    Chan S-K, Pöpperl H, Krumlauf R et al. An extradenticle-induced conformational change in a HOX protein overcomes an inhibitory function of the conserved hexapeptide motif. EMBO J 1996; 15:2476–2487.PubMedGoogle Scholar
  86. 86.
    Lohr U, Yussa M, Pick L. Drosophila fushi tarazu. a gene on the border of homeotic function. Curr Biol 2001; 11:1403–12.PubMedCrossRefGoogle Scholar
  87. 87.
    Lohr U, Pick L. Cofactor-interaction motifs and the cooption of a homeotic Hox protein into the segmentation pathway of Drosophila melanogaster. Curr Biol 2005; 15:643–9.PubMedCrossRefGoogle Scholar
  88. 88.
    Galant R, Walsh CM, Carroll SB. Hox repression of a target gene: extradenticle-independent, additive action through multiple monomer binding sites. Development 2002; 129:3115–26.PubMedGoogle Scholar
  89. 89.
    Medina-Martinez O, Ramirez-Solis R. In vivo mutagenesis of the Hoxb8 hexapeptide domain leads to dominant homeotic transformations that mimic the loss-of-function mutations in genes of the Hoxb cluster. Dev Biol 2003; 264:77–90.PubMedCrossRefGoogle Scholar
  90. 90.
    Merabet S, Kambris Z, Capovilla M et al. The hexapeptide and linker regions of the AbdA Hox protein regulate its activating and repressive functions. Dev Cell 2003; 4:761–8.PubMedCrossRefGoogle Scholar
  91. 91.
    Merabet S, Saadaoui M, Sambrani N et al. A unique Extradenticle recruitment mode in the Drosophila Hox protein Ultrabithorax. Proc Natl Acad Sci USA 2007; 104:16946–51.PubMedCrossRefGoogle Scholar
  92. 92.
    Prince F, Katsuyama T, Oshima Y et al. The YPWM motif links Antennapedia to the basal transcriptional machinery. Development 2008; 135:1669–79.PubMedCrossRefGoogle Scholar
  93. 93.
    Gebelein B, Culi J, Ryoo HD et al. Specificity of Distalless repression and limb primordia development by abdominal Hox proteins. Dev Cell 2002; 3:487–98.PubMedCrossRefGoogle Scholar
  94. 94.
    Chan SK, Jaffe L, Capovilla M et al. The DNA binding specificity of Ultrabithorax is modulated by cooperative interactions with extradenticle, another homeoprotein. Cell 1994; 78:603–15.PubMedCrossRefGoogle Scholar
  95. 95.
    Chan SK, Popperl H, Krumlauf R et al. An extradenticle-induced conformational change in a HOX protein overcomes an inhibitory function of the conserved hexapeptide motif. EMBO J 1996; 15:2476–87.PubMedGoogle Scholar
  96. 96.
    Qian YQ, Otting G, Furukubo-Tokunaga K et al. NMR structure determination reveals that the homeodomain is connected through a flexible linker to the main body in the Drosophila Antennapedia protein. Proc Natl Acad Sci USA 1992; 89:10738–10742.PubMedCrossRefGoogle Scholar
  97. 97.
    Johnson FB, Parker E, Krasnow MA. 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 USA 1995; 92:739–743.PubMedCrossRefGoogle Scholar
  98. 98.
    Bomze HM, Lopez AJ. Evolutionary conservation of the structure and expression of alternatively spliced Ultrabithorax isoforms from Drosophila. Genetics 1994; 136:965–77.PubMedGoogle Scholar
  99. 99.
    Lopez AJ, Hogness DS. Immunochemical dissection of the Ultrabithorax homeoprotein family in Drosophila melanogaster. Proc Natl Acad Sci Usa 1991; 88:9924–9928.PubMedCrossRefGoogle Scholar
  100. 100.
    Subramaniam V, Bomze HM, Lopez AJ. Functional differences between Ultrabithorax protein isoforms in Drosophila melanogaster: evidence from elimination, substitution and ectopic expression of specific isoforms. Genetics 1994; 136:979–91.PubMedGoogle Scholar
  101. 101.
    Yaron Y, McAdara JK, Lynch M et al. Identification of novel functional regions important for the activity of HOXB7 in mammalian cells. J Immunol 2001; 166:5058–67.PubMedGoogle Scholar
  102. 102.
    Zhao JJG, Lazzarini RA, Pick L. Functional dissection of the mouse Hox-a5 gene. EMBO J 1996; 15:1313–1322.PubMedGoogle Scholar
  103. 103.
    Vigano MA, Di Rocco G, Zappavigna V et al. Definition of the transcriptional activation domains of three human HOX proteins depends on the DNA-binding context. Mol Cell Biol 1998; 18:6201–12.PubMedGoogle Scholar
  104. 104.
    Tour E, Hittinger CT, McGinnis W. Evolutionarily conserved domains required for activation and repression functions of the Drosophila Hox protein Ultrabithorax. Development 2005; 132:5271–81.PubMedCrossRefGoogle Scholar
  105. 105.
    Rambaldi I, Kovacs EN, Featherstone MS. A proline-rich transcriptional activation domain in murine HOXD-4 (HOX-4.2). Nucleic Acids Res 1994; 22:376–82.PubMedCrossRefGoogle Scholar
  106. 106.
    Ronshaugen M, McGinnis N, McGinnis W. Hox protein mutation and macroevolution of the insect body plan. Nature 2002; 415:914–7.PubMedCrossRefGoogle Scholar
  107. 107.
    Galant R, Carroll SB. Evolution of a transcriptional repression domain in an insect Hox protein. Nature 2002; 415:910–3.PubMedCrossRefGoogle Scholar
  108. 108.
    Jaffe L, Ryoo HD, Mann RS. A role for phosphorylation by casein kinase II in modulating Antennapedia activity in Drosophila. Genes Dev 1997; 11:1327–40.PubMedCrossRefGoogle Scholar
  109. 109.
    Taghli-Lamallem O, Hsia C, Ronshaugen M et al. Context-dependent regulation of Hox protein functions by CK2 phosphorylation sites. Dev Genes Evol 2008; 218:321–32.PubMedCrossRefGoogle Scholar
  110. 110.
    Zhao X, Sun M, Zhao J et al. Mutations in HOXD13 underlie syndactyly type V and a novel brachydactyly-syndactyly syndrome. Am J Hum Genet 2007; 80:361–71.PubMedCrossRefGoogle Scholar
  111. 111.
    Utsch B, Becker K, Brock D et al. A novel stable polyalanine [poly(A)] expansion in the HOXA13 gene associated with hand-foot-genital syndrome: proper function of poly(A)-harbouring transcription factors depends on a critical repeat length? Hum Genet 2002; 110:488–94.PubMedCrossRefGoogle Scholar
  112. 112.
    Greer JM, Puetz J, Thomas KR et al. Maintenance of functional equivalence during paralogous Hox gene evolution. Nature 2000; 403:661–5.PubMedCrossRefGoogle Scholar

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© Landes Bioscience and Springer Science+Business Media 2010

Authors and Affiliations

  1. 1.Institute of Developmental Biology of Marseille LuminyUniversity of the MediterraneanMarseilleFrance

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