The PAX3 Paired Domain and Homeodomain Function as a Single Binding Module In Vivo to Regulate Subnuclear Localization and Mobility by a Mechanism That Requires Base-Specific Recognition

Journal of Molecular Biology

Volumn 402, Issue 1, 2010, Pages 178-193

  Corry, Gareth N ^a   Raghuram, Nikhil ^b   Missiaen, Kristal K ^b   Hu, Ninghe ^a   Hendzel, Michael J ^b   Underhill, D Alan ^a,b  

^a UNIVERSITY OF ALBERTA   (Canada)

^b CROSS CANCER INSTITUTE   (Canada)

Author keywords

Dynamics; Homeodomain; PAX; Subnuclear localization; Transcription factor

Indexed keywords

TRANSCRIPTION FACTOR PAX3; DNA; HOMEODOMAIN PROTEIN; NUCLEAR LOCALIZATION SIGNAL; PAIRED BOX TRANSCRIPTION FACTOR; PAX3 PROTEIN, HUMAN;

AMINO TERMINAL SEQUENCE; ANIMAL TISSUE; ARTICLE; CARBOXY TERMINAL SEQUENCE; CELL COMPARTMENTALIZATION; CELL NUCLEUS; CONTROLLED STUDY; DNA BINDING; EMBRYO; GENE MUTATION; HETEROCHROMATIN; IN VIVO STUDY; MOLECULAR RECOGNITION; NONHUMAN; PRIORITY JOURNAL; PROTEIN CONFORMATION; PROTEIN DOMAIN; PROTEIN LOCALIZATION; PROTEIN STRUCTURE; STRUCTURE ACTIVITY RELATION; WAARDENBURG SYNDROME; ANIMAL; ANIMAL EMBRYO; CELL CULTURE; CELL FRACTIONATION; CHEMISTRY; FIBROBLAST; GENETICS; HUMAN; METABOLISM; MOUSE; MUTATION; NUCLEAR LOCALIZATION SIGNAL; PROTEIN TERTIARY STRUCTURE;

ANIMALS; CELL NUCLEUS; CELLS, CULTURED; DNA; EMBRYO, MAMMALIAN; FIBROBLASTS; HOMEODOMAIN PROTEINS; HUMANS; MICE; MUTATION; NUCLEAR LOCALIZATION SIGNALS; PAIRED BOX TRANSCRIPTION FACTORS; PROTEIN STRUCTURE, TERTIARY; SUBCELLULAR FRACTIONS;

EID: 77956179941     PISSN: 00222836     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.jmb.2010.07.016     Document Type: Article

References (89)

1. Underhill D.A. Genetic and biochemical diversity in the Pax gene family. Biochem. Cell Biol. 2000, 78:629-638.
2. Chi N., Epstein J.A. Getting your Pax straight: Pax proteins in development and disease. Trends Genet. 2002, 18:41-47.
3. Czerny T., Schaffner G., Busslinger M. DNA sequence recognition by Pax proteins: bipartite structure of the paired domain and its binding site. Genes Dev. 1993, 7:2048-2061.
4. Xu H.E., Rould M.A., Xu W., Epstein J.A., Maas R.L., Pabo C.O. Crystal structure of the human Pax6 paired domain-DNA complex reveals specific roles for the linker region and carboxy-terminal subdomain in DNA binding. Genes Dev. 1999, 13:1263-1275.
5. Corry G.N., Underhill D.A. Pax3 target gene recognition occurs through distinct modes that are differentially affected by disease-associated mutations. Pigment Cell Res. 2005, 18:427-438.
6. Jun S., Desplan C. Cooperative interactions between paired domain and homeodomain. Development 1996, 122:2639-2650.
7. Apuzzo S., Abdelhakim A., Fortin A.S., Gros P. Cross-talk between the paired domain and the homeodomain of Pax3: DNA binding by each domain causes a structural change in the other domain, supporting interdependence for DNA binding. J. Biol. Chem. 2004, 279:33601-33612.
8. Apuzzo S., Gros P. The paired domain of Pax3 contains a putative homeodomain interaction pocket defined by cysteine scanning mutagenesis. Biochemistry 2006, 45:7154-7161.
9. Apuzzo S., Gros P. Site-specific modification of single cysteine Pax3 mutants reveals reciprocal regulation of DNA binding activity of the paired and homeo domain. Biochemistry 2002, 41:12076-12085.
10. Apuzzo S., Gros P. Cooperative interactions between the two DNA binding domains of Pax3: helix 2 of the paired domain is in the proximity of the amino terminus of the homeodomain. Biochemistry 2007, 46:2984-2993.
11. Fortin A.S., Underhill D.A., Gros P. Reciprocal effect of Waardenburg syndrome mutations on DNA binding by the Pax-3 paired domain and homeodomain. Hum. Mol. Genet. 1997, 6:1781-1790.
12. Fortin A.S., Underhill D.A., Gros P. Helix 2 of the paired domain plays a key role in the regulation of DNA-binding by the Pax-3 homeodomain. Nucleic Acids Res. 1998, 26:4574-4581.
13. Underhill D.A., Gros P. The paired-domain regulates DNA binding by the homeodomain within the intact Pax-3 protein. J. Biol. Chem. 1997, 272:14175-14182.
14. Underhill D.A., Vogan K.J., Gros P. Analysis of the mouse Splotch-delayed mutation indicates that the Pax-3 paired domain can influence homeodomain DNA-binding activity. Proc. Natl Acad. Sci. USA 1995, 92:3692-3696.
15. Baldwin C.T., Hoth C.F., Amos J.A., da-Silva E.O., Milunsky A. An exonic mutation in the HuP2 paired domain gene causes Waardenburg's syndrome. Nature 1992, 355:637-638.
16. Read A.P., Newton V.E. Waardenburg syndrome. J. Med. Genet. 1997, 34:656-665.
17. Tassabehji M., Read A.P., Newton V.E., Harris R., Balling R., Gruss P., Strachan T. Waardenburg's syndrome patients have mutations in the human homologue of the Pax-3 paired box gene. Nature 1992, 355:635-636. [see comments].
18. Corry G.N., Underhill D.A. PAX3 and Waardenburg syndrome type I. Inborn Errors of Development 2008, Oxford University Press, New York, NY. C. Epstein, R. Erikson, A. Wynshaw-Boris (Eds.).
19. Corry G.N., Hendzel M.J., Underhill D.A. Subnuclear localization and mobility are key indicators of PAX3 dysfunction in Waardenburg syndrome. Hum. Mol. Genet. 2008, 17:1825-1837.
20. Black B.E., Vitto M.J., Gioeli D., Spencer A., Afshar N., Conaway M.R., et al. Transient, ligand-dependent arrest of the androgen receptor in subnuclear foci alters phosphorylation and coactivator interactions. Mol. Endocrinol. 2004, 18:834-850.
21. Day R.N., Voss T.C., Enwright J.F., Booker C.F., Periasamy A., Schaufele F. Imaging the localized protein interactions between Pit-1 and the CCAAT/enhancer binding protein {alpha} in the living pituitary cell nucleus. Mol. Endocrinol. 2003, 17:333-345.
22. Enwright J.F., Kawecki-Crook M.A., Voss T.C., Schaufele F., Day R.N. A PIT-1 homeodomain mutant blocks the intranuclear recruitment of the CCAAT/enhancer binding protein alpha required for prolactin gene transcription. Mol. Endocrinol. 2003, 17:209-222.
23. Kawate H., Wu Y., Ohnaka K., Tao R.H., Nakamura K., Okabe T., et al. Impaired nuclear translocation, nuclear matrix targeting, and intranuclear mobility of mutant androgen receptors carrying amino acid substitutions in the deoxyribonucleic acid-binding domain derived from androgen insensitivity syndrome patients. J. Clin. Endocrinol. Metab. 2005, 90:6162-6169.
24. Rajaram N., Kerppola T.K. Synergistic transcription activation by Maf and Sox and their subnuclear localization are disrupted by a mutation in Maf that causes cataract. Mol. Cell. Biol. 2004, 24:5694-5709.
25. Farla P., Hersmus R., Geverts B., Mari P.O., Nigg A.L., Dubbink H.J., et al. The androgen receptor ligand-binding domain stabilizes DNA binding in living cells. J. Struct. Biol. 2004, 147:50-61.
26. Karpova T.S., Chen T.Y., Sprague B.L., McNally J.G. Dynamic interactions of a transcription factor with DNA are accelerated by a chromatin remodeller. EMBO Rep. 2004, 5:1064-1070.
27. Schaaf M.J., Cidlowski J.A. Molecular determinants of glucocorticoid receptor mobility in living cells: the importance of ligand affinity. Mol. Cell. Biol. 2003, 23:1922-1934.
28. Schaaf M.J., Willetts L., Hayes B.P., Maschera B., Stylianou E., Farrow S.N. The relationship between intranuclear mobility of the NF-kappaB subunit p65 and its DNA binding affinity. J. Biol. Chem. 2006, 281:22409-22420.
29. Sharp Z.D., Stenoien D.L., Mancini M.G., Ouspenski I.I., Mancini M.A. Inactivating Pit-1 mutations alter subnuclear dynamics suggesting a protein misfolding and nuclear stress response. J. Cell. Biochem. 2004, 92:664-678.
30. Birrane G., Soni A., Ladias J.A. Structural basis for DNA recognition by the human PAX3 homeodomain. Biochemistry 2009, 48:1148-1155.
31. Copley R.R. The EH1 motif in metazoan transcription factors. BMC Genomics 2005, 6:169.
32. Eberhard D., Jimenez G., Heavey B., Busslinger M. Transcriptional repression by pax5 (BSAP) through interaction with corepressors of the groucho family. EMBO J. 2000, 19:2292-2303. [in process citation].
33. Carrero G., Crawford E., Hendzel M.J., de Vries G. Characterizing fluorescence recovery curves for nuclear proteins undergoing binding events. Bull. Math. Biol. 2004, 66:1515-1545.
34. Carrero G., Crawford E., Th'ng J., de Vries G., Hendzel M.J. Quantification of protein-protein and protein-DNA interactions in vivo, using fluorescence recovery after photobleaching. Methods Enzymol. 2004, 375:415-442.
35. Raghuram N., Carrero G., Stasevich T.J., McNally J.G., Th'ng J., Hendzel M.J. Core histone hyperacetylation impacts cooperative behavior and high-affinity binding of histone H1 to chromatin. Biochemistry 2010, 49:4420-4431.
36. Dragan A.I., Li Z., Makeyeva E.N., Milgotina E.I., Liu Y., Crane-Robinson C., Privalov P.L. Forces driving the binding of homeodomains to DNA. Biochemistry 2006, 45:141-151.
37. Sekiya T., Muthurajan U.M., Luger K., Tulin A.V., Zaret K.S. Nucleosome-binding affinity as a primary determinant of the nuclear mobility of the pioneer transcription factor FoxA. Genes Dev. 2009, 23:804-809.
38. Hinow P., Rogers C.E., Barbieri C.E., Pietenpol J.A., Kenworthy A.K., DiBenedetto E. The DNA binding activity of p53 displays reaction-diffusion kinetics. Biophys. J. 2006, 91:330-342.
39. Iwahara J., Zweckstetter M., Clore G.M. NMR structural and kinetic characterization of a homeodomain diffusing and hopping on nonspecific DNA. Proc. Natl Acad. Sci. USA 2006, 103:15062-15067.
40. Iwahara J., Clore G.M. Detecting transient intermediates in macromolecular binding by paramagnetic NMR. Nature 2006, 440:1227-1230.
41. Berg O.G., Winter R.B., von Hippel P.H. Diffusion-driven mechanisms of protein translocation on nucleic acids: 1. Models and theory. Biochemistry 1981, 20:6929-6948.
42. von Hippel P.H., Berg O.G. Facilitated target location in biological systems. J. Biol. Chem. 1989, 264:675-678.
43. Berg O.G., von Hippel P.H. Selection of DNA binding sites by regulatory proteins. Statistical-mechanical theory and application to operators and promoters. J. Mol. Biol. 1987, 193:723-750.
44. von Hippel P.H., Berg O.G. On the specificity of DNA-protein interactions. Proc. Natl Acad. Sci. USA 1986, 83:1608-1612.
45. Slutsky M., Mirny L.A. Kinetics of protein-DNA interaction: facilitated target location in sequence-dependent potential. Biophys. J. 2004, 87:4021-4035.
46. Mancini M.G., Liu B., Sharp Z.D., Mancini M.A. Subnuclear partitioning and functional regulation of the Pit-1 transcription factor. J. Cell. Biochem. 1999, 72:322-338.
47. Bayes J.J., Malik H.S. Altered heterochromatin binding by a hybrid sterility protein in Drosophila sibling species. Science 2009, 326:1538-1541.
48. Wiggan O., Taniguchi-Sidle A., Hamel P.A. Interaction of the pRB-family proteins with factors containing paired-like homeodomains. Oncogene 1998, 16:227-236.
49. Magnaghi P., Roberts C., Lorain S., Lipinski M., Scambler P.J. HIRA, a mammalian homologue of Saccharomyces cerevisiae transcriptional co-repressors, interacts with Pax3. Nat. Genet. 1998, 20:74-77.
50. Zhang R., Poustovoitov M.V., Ye X., Santos H.A., Chen W., Daganzo S.M., et al. Formation of MacroH2A-containing senescence-associated heterochromatin foci and senescence driven by ASF1a and HIRA. Dev. Cell 2005, 8:19-30.
51. Ye X., Zerlanko B., Zhang R., Somaiah N., Lipinski M., Salomoni P., Adams P.D. Definition of pRB- and p53-dependent and -independent steps in HIRA/ASF1a-mediated formation of senescence-associated heterochromatin foci. Mol. Cell. Biol. 2007, 27:2452-2465.
52. Nielsen S.J., Schneider R., Bauer U.M., Bannister A.J., Morrison A., O'Carroll D., et al. Rb targets histone H3 methylation and HP1 to promoters. Nature 2001, 412:561-565.
53. Gonzalo S., Garcia-Cao M., Fraga M.F., Schotta G., Peters A.H., Cotter S.E., et al. Role of the RB1 family in stabilizing histone methylation at constitutive heterochromatin. Nat. Cell Biol. 2005, 7:420-428.
54. Isaac C.E., Francis S.M., Martens A.L., Julian L.M., Seifried L.A., Erdmann N., et al. The retinoblastoma protein regulates pericentric heterochromatin. Mol. Cell. Biol. 2006, 26:3659-3671.
55. Narita M., Nunez S., Heard E., Narita M., Lin A.W., Hearn S.A., et al. Rb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence. Cell 2003, 113:703-716.
56. Siddiqui H., Fox S.R., Gunawardena R.W., Knudsen E.S. Loss of RB compromises specific heterochromatin modifications and modulates HP1alpha dynamics. J. Cell Physiol. 2007, 211:131-137.
57. Cao Y., Wang C. The COOH-terminal transactivation domain plays a key role in regulating the in vitro and in vivo function of Pax3 homeodomain. J. Biol. Chem. 2000, 275:9854-9862.
58. Barr F.G., Galili N., Holick J., Biegel J.A., Rovera G., Emanuel B.S. Rearrangement of the PAX3 paired box gene in the paediatric solid tumour alveolar rhabdomyosarcoma. Nat. Genet. 1993, 3:113-117.
59. Galili N., Davis R.J., Fredericks W.J., Mukhopadhyay S., Rauscher F.J.D., Emanuel B.S., et al. Fusion of a fork head domain gene to PAX3 in the solid tumour alveolar rhabdomyosarcoma. Nat. Genet. 1993, 5:230-235. [published erratum appears in Nat. Genet. 6, 214 (1994)].
60. Shapiro D.N., Sublett J.E., Li B., Downing J.R., Naeve C.W. Fusion of PAX3 to a member of the forkhead family of transcription factors in human alveolar rhabdomyosarcoma. Cancer Res. 1993, 53:5108-5112.
61. Barber T.D., Barber M.C., Cloutier T.E., Friedman T.B. PAX3 gene structure, alternative splicing and evolution. Gene 1999, 237:311-319.
62. Bennicelli J.L., Edwards R.H., Barr F.G. Mechanism for transcriptional gain of function resulting from chromosomal translocation in alveolar rhabdomyosarcoma. Proc. Natl Acad. Sci. USA 1996, 93:5455-5459.
63. Amstutz R., Wachtel M., Troxler H., Kleinert P., Ebauer M., Haneke T., et al. Phosphorylation regulates transcriptional activity of PAX3/FKHR and reveals novel therapeutic possibilities. Cancer Res. 2008, 68:3767-3776.
64. Dietz K.N., Miller P.J., Hollenbach A.D. Phosphorylation of serine 205 by the protein kinase CK2 persists on Pax3-FOXO1, but not Pax3, throughout early myogenic differentiation. Biochemistry 2009, 48:11786-11795.
65. Miller P.J., Dietz K.N., Hollenbach A.D. Identification of serine 205 as a site of phosphorylation on Pax3 in proliferating but not differentiating primary myoblasts. Protein Sci. 2008, 17:1979-1986.
66. Galibert M.D., Yavuzer U., Dexter T.J., Goding C.R. Pax3 and regulation of the melanocyte-specific tyrosinase-related protein-1 promoter. J. Biol. Chem. 1999, 274:26894-26900.
67. Watanabe A., Takeda K., Ploplis B., Tachibana M. Epistatic relationship between Waardenburg syndrome genes MITF and PAX3. Nat. Genet. 1998, 18:283-286.
68. Lang D., Lu M.M., Huang L., Engleka K.A., Zhang M., Chu E.Y., et al. Pax3 functions at a nodal point in melanocyte stem cell differentiation. Nature 2005, 433:884-887.
69. Lang D., Chen F., Milewski R., Li J., Lu M.M., Epstein J.A. Pax3 is required for enteric ganglia formation and functions with Sox10 to modulate expression of c-ret. J. Clin. Invest. 2000, 106:963-971.
70. Lang D., Epstein J.A. Sox10 and Pax3 physically interact to mediate activation of a conserved c-RET enhancer. Hum. Mol. Genet. 2003, 12:937-945.
71. Bajard L., Relaix F., Lagha M., Rocancourt D., Daubas P., Buckingham M.E. A novel genetic hierarchy functions during hypaxial myogenesis: Pax3 directly activates Myf5 in muscle progenitor cells in the limb. Genes Dev. 2006, 20:2450-2464.
72. Buchberger A., Freitag D., Arnold H.H. A homeo-paired domain-binding motif directs Myf5 expression in progenitor cells of limb muscle. Development 2007, 134:1171-1180.
73. Lagha M., Kormish J.D., Rocancourt D., Manceau M., Epstein J.A., Zaret K.S., et al. Pax3 regulation of FGF signaling affects the progression of embryonic progenitor cells into the myogenic program. Genes Dev. 2008, 22:1828-1837.
74. Kwang S.J., Brugger S.M., Lazik A., Merrill A.E., Wu L.Y., Liu Y.H., et al. Msx2 is an immediate downstream effector of Pax3 in the development of the murine cardiac neural crest. Development 2002, 129:527-538.
75. Epstein J.A., Shapiro D.N., Cheng J., Lam P.Y., Maas R.L. Pax3 modulates expression of the c-Met receptor during limb muscle development. Proc. Natl Acad. Sci. USA 1996, 93:4213-4218.
76. Yang X.M., Vogan K., Gros P., Park M. Expression of the met receptor tyrosine kinase in muscle progenitor cells in somites and limbs is absent in Splotch mice. Development 1996, 122:2163-2171.
77. Mayanil C.S., Pool A., Nakazaki H., Reddy A.C., Mania-Farnell B., Yun B., et al. Regulation of murine TGFβ2 by Pax3 during early embryonic development. J. Biol. Chem. 2006, 281:24544-24552.
78. Wu M., Li J., Engleka K.A., Zhou B., Lu M.M., Plotkin J.B., Epstein J.A. Persistent expression of Pax3 in the neural crest causes cleft palate and defective osteogenesis in mice. J. Clin. Invest. 2008, 118:2076-2087.
79. Kallunki P., Jenkinson S., Edelman G.M., Jones F.S. Silencer elements modulate the expression of the gene for the neuron-glia cell adhesion molecule, Ng-CAM. J. Biol. Chem. 1995, 270:21291-21298.
80. Misteli T. Spatial positioning; a new dimension in genome function. Cell 2004, 119:153-156.
81. Parada L.A., McQueen P.G., Misteli T. Tissue-specific spatial organization of genomes. Genome Biol. 2004, 5:R44.
82. Phair R.D., Scaffidi P., Elbi C., Vecerova J., Dey A., Ozato K., et al. Global nature of dynamic protein-chromatin interactions in vivo: three-dimensional genome scanning and dynamic interaction networks of chromatin proteins. Mol. Cell. Biol. 2004, 24:6393-6402.
83. Misteli T. Beyond the sequence: cellular organization of genome function. Cell 2007, 128:787-800.
84. Misteli T. Protein dynamics: implications for nuclear architecture and gene expression. Science 2001, 291:843-847.
85. Zaidi S.K., Young D.W., Choi J.Y., Pratap J., Javed A., Montecino M., et al. The dynamic organization of gene-regulatory machinery in nuclear microenvironments. EMBO Rep. 2005, 6:128-133.
86. Stein G.S., van Wijnen A.J., Stein J.L., Lian J.B., Montecino M., Zaidi K., Javed A. Subnuclear organization and trafficking of regulatory proteins: implications for biological control and cancer. J. Cell. Biochem. Suppl. 2000, 35:84-92.
87. Corry G.N., Underhill D.A. Subnuclear compartmentalization of sequence-specific transcription factors and regulation of eukaryotic gene expression. Biochem. Cell Biol. 2005, 83:535-547.
88. Carmo-Fonseca M. The contribution of nuclear compartmentalization to gene regulation. Cell 2002, 108:513-521.
89. Kozlowski K., Walter M.A. Variation in residual PITX2 activity underlies the phenotypic spectrum of anterior segment developmental disorders. Hum. Mol. Genet. 2000, 9:2131-2139.