49. Rieckhof GE, Casares F, Ryoo HD, Abu-Shaar M, Mann RS (1997) Nuclear translocation of extradenticle requires homothorax, which encodes an extra- denticle-related homeodomain protein. Cell 91: 171–183. 50. Stobe P, Stein MA, Habring-Muller A, Bezdan D, Fuchs AL, et al. (2009) Multifactorial regulation of a hox target gene. PLoS Genet 5: e1000412. doi:10.1371/journal.pgen.1000412. 51. Joshi R, Passner JM, Rohs R, Jain R, Sosinsky A, et al. (2007) Functional specificity of a Hox protein mediated by the recognition of minor groove structure. Cell 131: 530–543. 52. Meijsing SH, Pufall MA, So AY, Bates DL, Chen L, et al. (2009) DNA binding site sequence directs glucocorticoid receptor structure and activity. Science 324: 407–410. 53. Lohr U, Pick L (2005) Cofactor-interaction motifs and the cooption of a homeotic Hox protein into the segmentation pathway of Drosophila melano- gaster. Curr Biol 15: 643–649. 54. Burke AC, Nelson CE, Morgan BA, Tabin C (1995) Hox genes and the evolution of vertebrate axial morphology. Development, in press. 55. Prud’homme B, Gompel N, Rokas A, Kassner VA, Williams TM, et al. (2006) Repeated morphological evolution through cis-regulatory changes in a pleiotropic gene. Nature 440: 1050–1053. 56. Gompel N, Prud’homme B, Wittkopp PJ, Kassner VA, Carroll SB (2005) Chance caught on the wing: cis-regulatory evolution and the origin of pigment patterns in Drosophila. Nature 433: 481–487. Protein Domains Driving Hox Protein Function 57. Jeong S, Rebeiz M, Andolfatto P, Werner T, True J, et al. (2008) The evolution of gene regulation underlies a morphological difference between two Drosophila sister species. Cell 132: 783–793. 58. Jeong S, Rokas A, Carroll SB (2006) Regulation of body pigmentation by the Abdominal-B Hox protein and its gain and loss in Drosophila evolution. Cell 125: 1387–1399. 59. Williams TM, Selegue JE, Werner T, Gompel N, Kopp A, et al. (2008) The regulation and evolution of a genetic switch controlling sexually dimorphic traits in Drosophila. Cell 134: 610–623. 60. Sivanantharajah L, Percival-Smith A (2009) Analysis of the sequence and phenotype of Drosophila Sex combs reduced alleles reveals potential functions of conserved protein motifs of the Sex combs reduced protein. Genetics 182: 191–203. 61. Hittinger CT, Stern DL, Carroll SB (2005) Pleiotropic functions of a conserved insect-specific Hox peptide motif. Development 132: 5261–5270. 62. Prince F, Katsuyama T, Oshima Y, Plaza S, Resendez-Perez D, et al. (2008) The YPWM motif links Antennapedia to the basal transcriptional machinery. Development 135: 1669–1679. 63. Saeed AI, Bhagabati NK, Braisted JC, Liang W, Sharov V, et al. (2006) TM4 microarray software suite. Methods Enzymol 411: 134–193. PLoS Genetics | www.plosgenetics.org 14 October 2011 | Volume 7 | Issue 10 | e1002302