Regulation of Hox target genes by a DNA bound Homothorax/Hox/Extradenticle complex.
To regulate their target genes, the Hox proteins of Drosophila often bind to DNA as heterodimers with the homeodomain protein Extradenticle (EXD). For EXD to bind DNA, it must be in the nucleus, and its nuclear localization requires a third homeodomain protein, Homothorax (HTH). Here we show that a conserved N-terminal domain of HTH directly binds to EXD in vitro, and is sufficient to induce the nuclear localization of EXD in vivo. However, mutating a key DNA binding residue in the HTH homeodomain abolishes many of its in vivo functions. HTH binds to DNA as part of a HTH/Hox/EXD trimeric complex, and we show that this complex is essential for the activation of a natural Hox target enhancer. Using a dominant negative form of HTH we provide evidence that similar complexes are important for several Hox- and exd-mediated functions in vivo. These data suggest that Hox proteins often function as part of a multiprotein complex, composed of HTH, Hox, and EXD proteins, bound to DNA.
Ryoo
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HD
Department of Biochemistry and Molecular Biophysics, Columbia University, HHSC 1108, New York, NY, USA.
Marty
T
T
Casares
F
F
Affolter
M
M
Mann
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RS
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D001692:Biological Transport; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism* / Q000502:physiology; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism; D004742:Enhancer Elements, Genetic / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000378:metabolism* / Q000502:physiology; D019476:Insect Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D019913:Nuclear Localization Signals; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000378:metabolism* / Q000502:physiology; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D019476:Insect Proteins; D019913:Nuclear Localization Signals; D014157:Transcription Factors; C083405:exd protein, Drosophila; C108704:hth protein, Drosophila; C059843:lab protein, Drosophila; D004247:DNA