Specificity for the Hairy/Enhancer of split Basic Helix-Loop-Helix (bHLH) Proteins Maps outside the bHLH Domain and Suggests Two Separable Modes of Transcriptional Repression

REFERENCES

• Benezra, R., R. L. Davis, D. Lockshon, D. L. Turner, and H. Weintraub. 1990. The protein Id, a negative regulator of helix-loop-helix DNA binding proteins. Cell 61:49–59.
   PubMed Web of Science ®Google Scholar
• Bier, E., H. Vässin, S. Younger-Shepherd, L. Y. Jan, and Y. N. Jan. 1992. deadpan, an essential pan-neural gene in Drosophila, encodes a helix-loop-helix protein similar to the hairy gene product. Genes Dev. 6:2137–2151.
   PubMed Web of Science ®Google Scholar
• Blackwell, T. K., J. Huang, A. Ma, L. Kretzner, F. W. Alt, R. N. Eisenman, and H. Weintraub. 1993. Binding of Myc proteins to canonical and nonca-nonical DNA sequences. Mol. Cell. Biol. 13:5216–5224.
   PubMed Web of Science ®Google Scholar
• Bopp, D., L. R. Bell, T. W. Cline, and P. Schedl. 1991. Developmental distribution of female-specific Sex-lethal proteins in Drosophila melanogaster. Genes Dev. 5:403–415.
   PubMed Web of Science ®Google Scholar
• Botas, J., J. Moscoso del Prado, and A. García-Bellido. 1982. Gene dose titration analysis in the search for trans-regulatory genes in Drosophila. EMBO J. 1:307–310.
   PubMedGoogle Scholar
• Cabrera, C. V., and M. C. Alonso. 1991. Transcriptional activation by het-erodimers of the achaete-scute and daughterless gene products of Drosophila. EMBO J. 10:2965–2973.
   PubMedGoogle Scholar
• Cabrera, C. V., M. C. Alonso, and H. Huikeshoven. 1994. Regulation of scute function by extramachrochaete in vitro and in vivo. Development 120:3595–3603.
   PubMedGoogle Scholar
• Cline, T. W. 1988. Evidence that sisterless-a and sisterless-b are two of several discrete numerator elements of the X/A sex determination signal in Dro-sophila that switch Sxl between two alternative stable expression states. Genetics 119:829–862.
   PubMed Web of Science ®Google Scholar
• Delidakis, C., and S. Artavanis-Tsakonas. 1992. The Enhancer of split [E(spl)] locus of Drosophila encodes seven independent helix-loop-helix proteins. Proc. Natl. Acad. Sci. USA 89:8731–8735.
   PubMedGoogle Scholar
• Ellis, H. M., D. R. Spann, and J. W. Posakony. 1990. extramacrochaetae, a negative regulator of sensory organ development in Drosophila, defines a new class of helix-loop-helix proteins. Cell 61:27–38.
   PubMedGoogle Scholar
• Erlich, H. A. 1989. PCR technology. Stockton Press, New York.
   Google Scholar
• Estes, P. A., L. N. Keyes, and P. Schedl. 1995. Multiple response elements in the Sex-lethal early promoter ensure its female-specific expression pattern. Mol. Cell. Biol. 15:904–917.
   PubMedGoogle Scholar
• Feder, J. N., L. Y. Jan, and Y. N. Jan. 1993. A rat gene with sequence homology to the Drosophila gene hairy is rapidly induced by growth factors known to influence neuronal differentiation. Mol. Cell. Biol. 13:105–113.
   PubMedGoogle Scholar
• Feder, J. N., L. Li, L. Y. Jan, and Y. N. Jan. 1994. Genomic cloning and chromosomal localization of HRY, the human homolog to the Drosophila segmentation gene, hairy. Genomics 20:56–61.
   PubMedGoogle Scholar
• Ferré-d'Amaré, A. R., G. C. Prendergast, E. B. Ziff, and S. K. Burley. 1993. Recognition by max of its cognate DNA through a dimeric b/HLH/z domain. Nature (London) 363:38–45.
   PubMed Web of Science ®Google Scholar
• Fitzpatrick, V. D., A. Percival-Smith, C. J. Ingles, and H. M. Krause. 1992. Homeodomain-independent activity of the fushi tarazu polypeptide in Dro-sophila embryos. Nature (London) 356:610–612.
   PubMedGoogle Scholar
• Garrell, J., and J. Modolell. 1990. The Drosophila extramacrochaetae locus, an antagonist of proneural genes that, like these genes, encodes a helix-loop-helix protein. Cell 61:39–48.
   PubMedGoogle Scholar
• Gray, S., P. Szymanski, and M. Levine. 1994. Short-range repression permits multiple enhancers to function autonomously within a complex promoter. Genes Dev. 8:1829–1838.
   PubMedGoogle Scholar
• Herschbach, B. M., and A. D. Johnson. 1993. Transcriptional repression in eukaryotes. Annu. Rev. Cell Biol. 9:479–509.
   PubMedGoogle Scholar
• Higuchi, R., B. Krummel, and R. K. Saiki. 1988. A general method of in vitro preparation and specific mutagenesis of DNA fragments: study of protein and DNA interactions. Nucleic Acids Res. 16:7351–7364.
   PubMed Web of Science ®Google Scholar
• Hiromi, Y., and W. J. Gehring. 1987. Regulation and function of the Dro-sophila segmentation gene fushi tarazu. Cell 50:963–974.
   PubMedGoogle Scholar
• Ingham, P., and J. P. Gergen. 1988. Interactions between the pair rule genes runt, hairy, even-skipped and fushi tarazu and the establishment of periodic pattern in the Drosophila embyo. Development 104(Suppl.):51–60.
   PubMedGoogle Scholar
• Ishibashi, M., Y. Sasai, S. Nakanishi, and R. Kageyama. 1993. Molecular characterization of HES-2, a mammalian helix-loop-helix factor structurally related to Drosophila hairy and Enhancer of split. Eur. J. Biochem. 215:645–652.
   PubMedGoogle Scholar
• Jürgens, G. 1987. Segmental organization of the tail region in the embryo of Drosophila melanogaster. A blastoderm fate map of the cuticle structures of the larval tail region. Roux's Arch. Dev. Biol. 196:141–157.
   PubMedGoogle Scholar
• Kagoshima, H., K. Shigesada, M. Satake, Y. Ito, H. Miyoshi, M. Ohki, M. Pepling, and P. Gergen. 1993. The Runt domain identifies a new family of heterodimeric transcriptional regulators. Trends Genet. 9:338–340.
   PubMedGoogle Scholar
• Klämbt, C., E. Knust, K. Tietze, and J. A. Campos-Ortega. 1989. Closely related transcripts encoded by the neurogenic gene complex Enhancer of split or Drosophila melanogaster. EMBO J. 8:203–210.
   PubMed Web of Science ®Google Scholar
• Knust, E., H. Schrons, F. Grawe, and J. A. Campos-Ortega. 1992. Seven genes of the Enhancer of split complex of Drosophila melanogaster encode helix-loop-helix proteins. Genetics 132:505–518.
   PubMedGoogle Scholar
• Levine, M., and J. L. Manley. 1989. Transcriptional repression of eukaryotic promoters. Cell 59:405–408.
   PubMedGoogle Scholar
• Martínez, C., J. Modolell, and J. Garrell. 1993. Regulation of the proneural gene achaete by helix-loop-helix proteins. Mol. Cell. Biol. 13:3514–3521.
   PubMedGoogle Scholar
• Murre, C., P. S. McCaw, and D. Baltimore. 1989. A new DNA binding and dimerisation motif in immunoglobulin enhancer binding, daughterless, MyoD, and myc proteins. Cell 56:777–783.
   PubMed Web of Science ®Google Scholar
• Murre, C., P. S. McCaw, H. Vässin, M. Caudy, L. Y. Jan, Y. N. Jan, C. V. Cabrera, J. N. Buskin, S. D. Hauschka, A. B. Lassar, H. Weintraub, and D. Baltimore. 1989. Interactions between heterologous helix-loop-helix proteins generate complexes that bind specifically to a common DNA sequence. Cell 58:537–544.
   PubMed Web of Science ®Google Scholar
• Ohsako, S., J. Hyer, G. Panganiban, I. Oliver, and M. Caudy. 1994. hairy functions as a DNA-binding helix-loop-helix repressor of Drosophila sensory organ formation. Genes Dev. 8:2743–2755.
   PubMedGoogle Scholar
• Parkhurst, S. M., D. Bopp, and D. Ish-Horowicz. 1990. X:A ratio is trans-duced by helix-loop-helix proteins in Drosophila. Cell 63:1179–1191.
   PubMedGoogle Scholar
• Parkhurst, S. M., S. R. Dawson, and G. Poortinga. Unpublished data.
   Google Scholar
• Parkhurst, S. M., and D. Ish-Horowicz. 1991. Mis-regulating segmentation gene expression in Drosophila. Development 111:1121–1135.
   PubMedGoogle Scholar
• Parkhurst, S. M., H. D. Lipshitz, and D. Ish-Horowicz. 1993. achaete-scute feminizing activities and Drosophila sex-determination. Development 117: 737–749.
   PubMedGoogle Scholar
• Parkhurst, S. M., and P. M. Meneely. 1994. Sex determination and dosage compensation: lessons from flies and worms. Science 264:924–932.
   PubMedGoogle Scholar
• Paroush, Z., R. L. Finley, T. Kidd, S. M. Wainwright, P. W. Ingham, R. Brent, and D. Ish-Horowicz. 1994. Groucho is required for Drosophila neu-rogenesis, segmentation and sex-determination, and interacts directly with Hairy-related bHLH proteins. Cell 79:805–815.
   PubMed Web of Science ®Google Scholar
• Rushlow, C. A., A. Hogan, S. M. Pinchin, K. M. Howe, M. T. Lardelli, and D. Ish-Horowicz. 1989. The Drosophila hairy protein acts in both segmentation and bristle patterning and shows homology to N-myc. EMBO J. 8:3095–3103.
   PubMedGoogle Scholar
• Sambrook, J., E. F. Fritsch, and T. Maniatis. 1989. Molecular cloning: a laboratory manual. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y.
   Google Scholar
• Sasai, Y., R. Kageyama, Y. Tagawa, R. Shigemoto, and S. Nakanishi. 1992. Two mammalian helix loop helix factors structurally related to Drosophila hairy and Enhancer-of-split. Genes Dev. 6:2620–2634.
   PubMed Web of Science ®Google Scholar
• Shoop, R., and S. M. Parkhurst. Unpublished data.
   Google Scholar
• Stifani, S., C. M. Blaumueller, N. J. Redhead, R. E. Hill, and S. Artavanis-Tsakonas. 1992. Human homologs of a Drosophila Enhancer of split gene product define a novel family of nuclear proteins. Nat. Genet. 2:119–127.
   PubMed Web of Science ®Google Scholar
• Tautz, D., and C. Pfeifle. 1989. A non-radioactive in situ hybridization method for the localization of specific RNAs in Drosophila embryos reveals translational control of the segmentation gene hunchback. Chromosoma 98:81–85.
   PubMed Web of Science ®Google Scholar
• Tietze, K., N. Oellers, and E. Knust. 1992. Enhancer of splitD, a dominant mutation of Drosophila, and its use in the study of functional domains of a helix-loop-helix protein. Proc. Natl. Acad. Sci. USA 89:6152–6156.
   PubMedGoogle Scholar
• Tietze, K., H. Schrons, J. A. Campos-Ortega, and E. Knust. 1993. A functional analysis of the genes Enhancer of split and HLH-m5 during early neurogenesis in Drosophila melanogaster. Roux's Arch. Dev. Biol. 203:10–17.
   Google Scholar
• Torres, M., and L. Sánchez. 1989. The scute (T4) gene acts as a numerator element of the X:A signal that determines the state of activity of Sex-lethal in Drosophila. EMBO J. 8:3079–3086.
   PubMed Web of Science ®Google Scholar
• Turner, D. L., and H. Weintraub. Unpublished data.
   Google Scholar
• Van Doren, M., A. M. Bailey, J. Esnayra, K. Ede, and J. W. Posakony. 1994. Negative regulation of proneural gene activity: hairy is a direct transcriptional repressor of achaete. Genes Dev. 8:2729–2742.
   PubMedGoogle Scholar
• Van Doren, M., H. M. Ellis, and J. W. Posakony. 1991. The Drosophila extramacrochaetae protein antagonizes sequence-specific DNA binding by daughterless/achaete-scute protein complex. Development 113:245–255.
   PubMedGoogle Scholar
• Wainwright, S. M., and D. Ish-Horowicz. 1992. Point mutations in the Dro-sophila hairy gene demonstrate in vivo requirements for basic, helix-loop-helix, and WRPW domains. Mol. Cell. Biol. 12:2475–2483.
   PubMedGoogle Scholar
• Weintraub, H., R. Davis, S. Tapscott, M. Thayer, M. Krause, R. Benezra, T. K. Blackwell, D. Turner, R. Rupp, S. Hollenberg, Y. Zhuang, and A. Lassar. 1991. The MyoD gene family: nodal point during specification of the muscle cell lineage. Science 251:761–766.
   PubMed Web of Science ®Google Scholar
• Younger-Shepherd, S., H. Vaessin, E. Bier, L. Y. Jan, and Y. N. Jan. 1992. deadpan, an essential pan-neural gene encoding an HLH protein, acts as a denominator in Drosophila sex determination. Cell 70:911–922.
   PubMedGoogle Scholar