Skip to main content
NCBI home page
Genetics logoLink to Genetics
. 2003 Nov;165(3):1355–1384. doi: 10.1093/genetics/165.3.1355

A theoretical model for the regulation of Sex-lethal, a gene that controls sex determination and dosage compensation in Drosophila melanogaster.

Matthieu Louis 1, Liisa Holm 1, Lucas Sánchez 1, Marcelle Kaufman 1
PMCID: PMC1462829  PMID: 14668388

Abstract

Cell fate commitment relies upon making a choice between different developmental pathways and subsequently remembering that choice. Experimental studies have thoroughly investigated this central theme in biology for sex determination. In the somatic cells of Drosophila melanogaster, Sex-lethal (Sxl) is the master regulatory gene that specifies sexual identity. We have developed a theoretical model for the initial sex-specific regulation of Sxl expression. The model is based on the well-documented molecular details of the system and uses a stochastic formulation of transcription. Numerical simulations allow quantitative assessment of the role of different regulatory mechanisms in achieving a robust switch. We establish on a formal basis that the autoregulatory loop involved in the alternative splicing of Sxl primary transcripts generates an all-or-none bistable behavior and constitutes an efficient stabilization and memorization device. The model indicates that production of a small amount of early Sxl proteins leaves the autoregulatory loop in its off state. Numerical simulations of mutant genotypes enable us to reproduce and explain the phenotypic effects of perturbations induced in the dosage of genes whose products participate in the early Sxl promoter activation.

Full Text

The Full Text of this article is available as a PDF (607.6 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arkin A., Ross J., McAdams H. H. Stochastic kinetic analysis of developmental pathway bifurcation in phage lambda-infected Escherichia coli cells. Genetics. 1998 Aug;149(4):1633–1648. doi: 10.1093/genetics/149.4.1633. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bachiller D., Sánchez L. Production of X0 clones in XX females of Drosophila. Genet Res. 1991 Feb;57(1):23–28. doi: 10.1017/s0016672300028998. [DOI] [PubMed] [Google Scholar]
  3. Barbash D. A., Cline T. W. Genetic and molecular analysis of the autosomal component of the primary sex determination signal of Drosophila melanogaster. Genetics. 1995 Dec;141(4):1451–1471. doi: 10.1093/genetics/141.4.1451. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bashirullah A., Halsell S. R., Cooperstock R. L., Kloc M., Karaiskakis A., Fisher W. W., Fu W., Hamilton J. K., Etkin L. D., Lipshitz H. D. Joint action of two RNA degradation pathways controls the timing of maternal transcript elimination at the midblastula transition in Drosophila melanogaster. EMBO J. 1999 May 4;18(9):2610–2620. doi: 10.1093/emboj/18.9.2610. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bell L. R., Horabin J. I., Schedl P., Cline T. W. Positive autoregulation of sex-lethal by alternative splicing maintains the female determined state in Drosophila. Cell. 1991 Apr 19;65(2):229–239. doi: 10.1016/0092-8674(91)90157-t. [DOI] [PubMed] [Google Scholar]
  6. Bell L. R., Maine E. M., Schedl P., Cline T. W. Sex-lethal, a Drosophila sex determination switch gene, exhibits sex-specific RNA splicing and sequence similarity to RNA binding proteins. Cell. 1988 Dec 23;55(6):1037–1046. doi: 10.1016/0092-8674(88)90248-6. [DOI] [PubMed] [Google Scholar]
  7. Bernstein M., Cline T. W. Differential effects of Sex-lethal mutations on dosage compensation early in Drosophila development. Genetics. 1994 Mar;136(3):1051–1061. doi: 10.1093/genetics/136.3.1051. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Bernstein M., Lersch R. A., Subrahmanyan L., Cline T. W. Transposon insertions causing constitutive Sex-lethal activity in Drosophila melanogaster affect Sxl sex-specific transcript splicing. Genetics. 1995 Feb;139(2):631–648. doi: 10.1093/genetics/139.2.631. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Bier E., Vaessin H., Younger-Shepherd S., Jan L. Y., Jan Y. N. deadpan, an essential pan-neural gene in Drosophila, encodes a helix-loop-helix protein similar to the hairy gene product. Genes Dev. 1992 Nov;6(11):2137–2151. doi: 10.1101/gad.6.11.2137. [DOI] [PubMed] [Google Scholar]
  10. Bopp D., Bell L. R., Cline T. W., Schedl P. Developmental distribution of female-specific Sex-lethal proteins in Drosophila melanogaster. Genes Dev. 1991 Mar;5(3):403–415. doi: 10.1101/gad.5.3.403. [DOI] [PubMed] [Google Scholar]
  11. Botella L. M., Doñoro C., Sánchez L., Segarra C., Granadino B. Cloning and characterization of the scute (sc) gene of Drosophila subobscura. Genetics. 1996 Nov;144(3):1043–1051. doi: 10.1093/genetics/144.3.1043. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Bridges C. B. TRIPLOID INTERSEXES IN DROSOPHILA MELANOGASTER. Science. 1921 Sep 16;54(1394):252–254. doi: 10.1126/science.54.1394.252. [DOI] [PubMed] [Google Scholar]
  13. Cabrera C. V., Alonso M. C. Transcriptional activation by heterodimers of the achaete-scute and daughterless gene products of Drosophila. EMBO J. 1991 Oct;10(10):2965–2973. doi: 10.1002/j.1460-2075.1991.tb07847.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Cao D., Parker R. Computational modeling of eukaryotic mRNA turnover. RNA. 2001 Sep;7(9):1192–1212. doi: 10.1017/s1355838201010330. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Carillo S., Pariat M., Steff A. M., Roux P., Etienne-Julan M., Lorca T., Piechaczyk M. Differential sensitivity of FOS and JUN family members to calpains. Oncogene. 1994 Jun;9(6):1679–1689. [PubMed] [Google Scholar]
  16. Cline T. W. A female-specific lethal lesion in an X-linked positive regulator of the Drosophila sex determination gene, Sex-lethal. Genetics. 1986 Jul;113(3):641–663. doi: 10.1093/genetics/113.3.641. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Cline T. W. Autoregulatory functioning of a Drosophila gene product that establish es and maintains the sexually determined state. Genetics. 1984 Jun;107(2):231–277. doi: 10.1093/genetics/107.2.231. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Cline T. W. Evidence that sisterless-a and sisterless-b are two of several discrete "numerator elements" of the X/A sex determination signal in Drosophila that switch Sxl between two alternative stable expression states. Genetics. 1988 Aug;119(4):829–862. doi: 10.1093/genetics/119.4.829. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Cline T. W. Maternal and zygotic sex-specific gene interactions in Drosophila melanogaster. Genetics. 1980 Dec;96(4):903–926. doi: 10.1093/genetics/96.4.903. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Cline T. W., Meyer B. J. Vive la différence: males vs females in flies vs worms. Annu Rev Genet. 1996;30:637–702. doi: 10.1146/annurev.genet.30.1.637. [DOI] [PubMed] [Google Scholar]
  21. Cline T. W. The interaction between daughterless and sex-lethal in triploids: a lethal sex-transforming maternal effect linking sex determination and dosage compensation in Drosophila melanogaster. Dev Biol. 1983 Feb;95(2):260–274. doi: 10.1016/0012-1606(83)90027-1. [DOI] [PubMed] [Google Scholar]
  22. Cline T. W. Two closely linked mutations in Drosophila melanogaster that are lethal to opposite sexes and interact with daughterless. Genetics. 1978 Dec;90(4):683–698. doi: 10.1093/genetics/90.4.683. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Cook D. L., Gerber A. N., Tapscott S. J. Modeling stochastic gene expression: implications for haploinsufficiency. Proc Natl Acad Sci U S A. 1998 Dec 22;95(26):15641–15646. doi: 10.1073/pnas.95.26.15641. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Cronmiller C., Schedl P., Cline T. W. Molecular characterization of daughterless, a Drosophila sex determination gene with multiple roles in development. Genes Dev. 1988 Dec;2(12A):1666–1676. doi: 10.1101/gad.2.12a.1666. [DOI] [PubMed] [Google Scholar]
  25. Davis R. L., Cheng P. F., Lassar A. B., Weintraub H. The MyoD DNA binding domain contains a recognition code for muscle-specific gene activation. Cell. 1990 Mar 9;60(5):733–746. doi: 10.1016/0092-8674(90)90088-v. [DOI] [PubMed] [Google Scholar]
  26. Dawson S. R., Turner D. L., Weintraub H., Parkhurst S. M. 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. Mol Cell Biol. 1995 Dec;15(12):6923–6931. doi: 10.1128/mcb.15.12.6923. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Deshpande G., Stukey J., Schedl P. scute (sis-b) function in Drosophila sex determination. Mol Cell Biol. 1995 Aug;15(8):4430–4440. doi: 10.1128/mcb.15.8.4430. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Dundr M., Misteli T. Functional architecture in the cell nucleus. Biochem J. 2001 Jun 1;356(Pt 2):297–310. doi: 10.1042/0264-6021:3560297. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Elowitz Michael B., Levine Arnold J., Siggia Eric D., Swain Peter S. Stochastic gene expression in a single cell. Science. 2002 Aug 16;297(5584):1183–1186. doi: 10.1126/science.1070919. [DOI] [PubMed] [Google Scholar]
  30. Emery J. F., Bier E. Specificity of CNS and PNS regulatory subelements comprising pan-neural enhancers of the deadpan and scratch genes is achieved by repression. Development. 1995 Nov;121(11):3549–3560. doi: 10.1242/dev.121.11.3549. [DOI] [PubMed] [Google Scholar]
  31. Estes P. A., Keyes L. N., Schedl P. Multiple response elements in the Sex-lethal early promoter ensure its female-specific expression pattern. Mol Cell Biol. 1995 Feb;15(2):904–917. doi: 10.1128/mcb.15.2.904. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Factor P., Senne C., Ridge K., Jaffe H. A., Blanco G., Mercer R. W., Sznajder J. I. Effects of adenoviral mediated transfer of Na+,K(+)-ATPase subunit genes to alveolar epithelial cells. Ann N Y Acad Sci. 1997 Nov 3;834:104–106. doi: 10.1111/j.1749-6632.1997.tb52231.x. [DOI] [PubMed] [Google Scholar]
  33. Fiering S., Whitelaw E., Martin D. I. To be or not to be active: the stochastic nature of enhancer action. Bioessays. 2000 Apr;22(4):381–387. doi: 10.1002/(SICI)1521-1878(200004)22:4<381::AID-BIES8>3.0.CO;2-E. [DOI] [PubMed] [Google Scholar]
  34. Gergen J. P. Dosage Compensation in Drosophila: Evidence That daughterless and Sex-lethal Control X Chromosome Activity at the Blastoderm Stage of Embryogenesis. Genetics. 1987 Nov;117(3):477–485. doi: 10.1093/genetics/117.3.477. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Hargrove J. L., Hulsey M. G., Beale E. G. The kinetics of mammalian gene expression. Bioessays. 1991 Dec;13(12):667–674. doi: 10.1002/bies.950131209. [DOI] [PubMed] [Google Scholar]
  36. Hargrove J. L., Schmidt F. H. The role of mRNA and protein stability in gene expression. FASEB J. 1989 Oct;3(12):2360–2370. doi: 10.1096/fasebj.3.12.2676679. [DOI] [PubMed] [Google Scholar]
  37. Herschlag D., Johnson F. B. Synergism in transcriptional activation: a kinetic view. Genes Dev. 1993 Feb;7(2):173–179. doi: 10.1101/gad.7.2.173. [DOI] [PubMed] [Google Scholar]
  38. Heuer K. H., Mackay J. P., Podzebenko P., Bains N. P., Weiss A. S., King G. F., Easterbrook-Smith S. B. Development of a sensitive peptide-based immunoassay: application to detection of the Jun and Fos oncoproteins. Biochemistry. 1996 Jul 16;35(28):9069–9075. doi: 10.1021/bi952817o. [DOI] [PubMed] [Google Scholar]
  39. Horabin J. I., Schedl P. Splicing of the drosophila Sex-lethal early transcripts involves exon skipping that is independent of Sex-lethal protein. RNA. 1996 Jan;2(1):1–10. [PMC free article] [PubMed] [Google Scholar]
  40. Hoshijima K., Kohyama A., Watakabe I., Inoue K., Sakamoto H., Shimura Y. Transcriptional regulation of the Sex-lethal gene by helix-loop-helix proteins. Nucleic Acids Res. 1995 Sep 11;23(17):3441–3448. doi: 10.1093/nar/23.17.3441. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Hume D. A. Probability in transcriptional regulation and its implications for leukocyte differentiation and inducible gene expression. Blood. 2000 Oct 1;96(7):2323–2328. [PubMed] [Google Scholar]
  42. Jackson D. A., Pombo A., Iborra F. The balance sheet for transcription: an analysis of nuclear RNA metabolism in mammalian cells. FASEB J. 2000 Feb;14(2):242–254. [PubMed] [Google Scholar]
  43. Jinks T. M., Polydorides A. D., Calhoun G., Schedl P. The JAK/STAT signaling pathway is required for the initial choice of sexual identity in Drosophila melanogaster. Mol Cell. 2000 Mar;5(3):581–587. doi: 10.1016/s1097-2765(00)80451-7. [DOI] [PubMed] [Google Scholar]
  44. Kanaar R., Lee A. L., Rudner D. Z., Wemmer D. E., Rio D. C. Interaction of the sex-lethal RNA binding domains with RNA. EMBO J. 1995 Sep 15;14(18):4530–4539. doi: 10.1002/j.1460-2075.1995.tb00132.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Katsamba P. S., Myszka D. G., Laird-Offringa I. A. Two functionally distinct steps mediate high affinity binding of U1A protein to U1 hairpin II RNA. J Biol Chem. 2001 Apr 10;276(24):21476–21481. doi: 10.1074/jbc.M101624200. [DOI] [PubMed] [Google Scholar]
  46. Kennell D., Riezman H. Transcription and translation initiation frequencies of the Escherichia coli lac operon. J Mol Biol. 1977 Jul;114(1):1–21. doi: 10.1016/0022-2836(77)90279-0. [DOI] [PubMed] [Google Scholar]
  47. Keyes L. N., Cline T. W., Schedl P. The primary sex determination signal of Drosophila acts at the level of transcription. Cell. 1992 Mar 6;68(5):933–943. doi: 10.1016/0092-8674(92)90036-c. [DOI] [PubMed] [Google Scholar]
  48. Kierzek A. M., Zaim J., Zielenkiewicz P. The effect of transcription and translation initiation frequencies on the stochastic fluctuations in prokaryotic gene expression. J Biol Chem. 2000 Nov 2;276(11):8165–8172. doi: 10.1074/jbc.M006264200. [DOI] [PubMed] [Google Scholar]
  49. Kramer S. G., Jinks T. M., Schedl P., Gergen J. P. Direct activation of Sex-lethal transcription by the Drosophila runt protein. Development. 1999 Jan;126(1):191–200. doi: 10.1242/dev.126.1.191. [DOI] [PubMed] [Google Scholar]
  50. Laird-Offringa I. A., Belasco J. G. Analysis of RNA-binding proteins by in vitro genetic selection: identification of an amino acid residue important for locking U1A onto its RNA target. Proc Natl Acad Sci U S A. 1995 Dec 5;92(25):11859–11863. doi: 10.1073/pnas.92.25.11859. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Lazarides E., Woods C. Biogenesis of the red blood cell membrane-skeleton and the control of erythroid morphogenesis. Annu Rev Cell Biol. 1989;5:427–452. doi: 10.1146/annurev.cb.05.110189.002235. [DOI] [PubMed] [Google Scholar]
  52. Lecuit T., Wieschaus E. Polarized insertion of new membrane from a cytoplasmic reservoir during cleavage of the Drosophila embryo. J Cell Biol. 2000 Aug 21;150(4):849–860. doi: 10.1083/jcb.150.4.849. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Liu Y., Belote J. M. Protein-protein interactions among components of the Drosophila primary sex determination signal. Mol Gen Genet. 1995 Jul 28;248(2):182–189. doi: 10.1007/BF02190799. [DOI] [PubMed] [Google Scholar]
  54. Lucchesi J. C. Dosage compensation in Drosophila and the "complex' world of transcriptional regulation. Bioessays. 1996 Jul;18(7):541–547. doi: 10.1002/bies.950180705. [DOI] [PubMed] [Google Scholar]
  55. Massari M. E., Murre C. Helix-loop-helix proteins: regulators of transcription in eucaryotic organisms. Mol Cell Biol. 2000 Jan;20(2):429–440. doi: 10.1128/mcb.20.2.429-440.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. McAdams H. H., Arkin A. It's a noisy business! Genetic regulation at the nanomolar scale. Trends Genet. 1999 Feb;15(2):65–69. doi: 10.1016/s0168-9525(98)01659-x. [DOI] [PubMed] [Google Scholar]
  57. Meise M., Hilfiker-Kleiner D., Dübendorfer A., Brunner C., Nöthiger R., Bopp D. Sex-lethal, the master sex-determining gene in Drosophila, is not sex-specifically regulated in Musca domestica. Development. 1998 Apr;125(8):1487–1494. doi: 10.1242/dev.125.8.1487. [DOI] [PubMed] [Google Scholar]
  58. Murre C., McCaw P. S., Vaessin H., Caudy M., Jan L. Y., Jan Y. N., Cabrera C. V., Buskin J. N., Hauschka S. D., Lassar A. B. Interactions between heterologous helix-loop-helix proteins generate complexes that bind specifically to a common DNA sequence. Cell. 1989 Aug 11;58(3):537–544. doi: 10.1016/0092-8674(89)90434-0. [DOI] [PubMed] [Google Scholar]
  59. Paal K., Baeuerle P. A., Schmitz M. L. Basal transcription factors TBP and TFIIB and the viral coactivator E1A 13S bind with distinct affinities and kinetics to the transactivation domain of NF-kappaB p65. Nucleic Acids Res. 1997 Mar 1;25(5):1050–1055. doi: 10.1093/nar/25.5.1050. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Parkhurst S. M., Bopp D., Ish-Horowicz D. X:A ratio, the primary sex-determining signal in Drosophila, is transduced by helix-loop-helix proteins. Cell. 1990 Dec 21;63(6):1179–1191. doi: 10.1016/0092-8674(90)90414-a. [DOI] [PubMed] [Google Scholar]
  61. Penalva L. O., Sakamoto H., Navarro-Sabaté A., Sakashita E., Granadino B., Segarra C., Sánchez L. Regulation of the gene Sex-lethal: a comparative analysis of Drosophila melanogaster and Drosophila subobscura. Genetics. 1996 Dec;144(4):1653–1664. doi: 10.1093/genetics/144.4.1653. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Pultz M. A., Baker B. S. The dual role of hermaphrodite in the Drosophila sex determination regulatory hierarchy. Development. 1995 Jan;121(1):99–111. doi: 10.1242/dev.121.1.99. [DOI] [PubMed] [Google Scholar]
  63. Saccone G., Peluso I., Artiaco D., Giordano E., Bopp D., Polito L. C. The Ceratitis capitata homologue of the Drosophila sex-determining gene sex-lethal is structurally conserved, but not sex-specifically regulated. Development. 1998 Apr;125(8):1495–1500. doi: 10.1242/dev.125.8.1495. [DOI] [PubMed] [Google Scholar]
  64. Salz H. K., Maine E. M., Keyes L. N., Samuels M. E., Cline T. W., Schedl P. The Drosophila female-specific sex-determination gene, Sex-lethal, has stage-, tissue-, and sex-specific RNAs suggesting multiple modes of regulation. Genes Dev. 1989 May;3(5):708–719. doi: 10.1101/gad.3.5.708. [DOI] [PubMed] [Google Scholar]
  65. Samuels M. E., Schedl P., Cline T. W. The complex set of late transcripts from the Drosophila sex determination gene sex-lethal encodes multiple related polypeptides. Mol Cell Biol. 1991 Jul;11(7):3584–3602. doi: 10.1128/mcb.11.7.3584. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Samuels M., Deshpande G., Schedl P. Activities of the Sex-lethal protein in RNA binding and protein:protein interactions. Nucleic Acids Res. 1998 Jun 1;26(11):2625–2637. doi: 10.1093/nar/26.11.2625. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Sefton L., Timmer J. R., Zhang Y., Béranger F., Cline T. W. An extracellular activator of the Drosophila JAK/STAT pathway is a sex-determination signal element. Nature. 2000 Jun 22;405(6789):970–973. doi: 10.1038/35016119. [DOI] [PubMed] [Google Scholar]
  68. Sun X. H., Baltimore D. An inhibitory domain of E12 transcription factor prevents DNA binding in E12 homodimers but not in E12 heterodimers. Cell. 1991 Jan 25;64(2):459–470. doi: 10.1016/0092-8674(91)90653-g. [DOI] [PubMed] [Google Scholar]
  69. Sánchez L., Nöthiger R. Sex determination and dosage compensation in Drosophila melanogaster: production of male clones in XX females. EMBO J. 1983;2(4):485–491. doi: 10.1002/j.1460-2075.1983.tb01451.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  70. Torres M., Sánchez L. 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. 1989 Oct;8(10):3079–3086. doi: 10.1002/j.1460-2075.1989.tb08459.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  71. Torres M., Sánchez L. The segmentation gene runt is needed to activate Sex-lethal, a gene that controls sex determination and dosage compensation in Drosophila. Genet Res. 1992 Jun;59(3):189–198. doi: 10.1017/s0016672300030470. [DOI] [PubMed] [Google Scholar]
  72. Torres M., Sánchez L. The sisterless-b function of the Drosophila gene scute is restricted to the stage when the X:A ratio determines the activity of Sex-lethal. Development. 1991 Oct;113(2):715–722. doi: 10.1242/dev.113.2.715. [DOI] [PubMed] [Google Scholar]
  73. Van Doren M., Ellis H. M., Posakony J. W. The Drosophila extramacrochaetae protein antagonizes sequence-specific DNA binding by daughterless/achaete-scute protein complexes. Development. 1991 Sep;113(1):245–255. doi: 10.1242/dev.113.1.245. [DOI] [PubMed] [Google Scholar]
  74. Varani G., Nagai K. RNA recognition by RNP proteins during RNA processing. Annu Rev Biophys Biomol Struct. 1998;27:407–445. doi: 10.1146/annurev.biophys.27.1.407. [DOI] [PubMed] [Google Scholar]
  75. Vieille C., Zeikus G. J. Hyperthermophilic enzymes: sources, uses, and molecular mechanisms for thermostability. Microbiol Mol Biol Rev. 2001 Mar;65(1):1–43. doi: 10.1128/MMBR.65.1.1-43.2001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  76. Voronova A., Baltimore D. Mutations that disrupt DNA binding and dimer formation in the E47 helix-loop-helix protein map to distinct domains. Proc Natl Acad Sci U S A. 1990 Jun;87(12):4722–4726. doi: 10.1073/pnas.87.12.4722. [DOI] [PMC free article] [PubMed] [Google Scholar]
  77. Walters M. C., Fiering S., Eidemiller J., Magis W., Groudine M., Martin D. I. Enhancers increase the probability but not the level of gene expression. Proc Natl Acad Sci U S A. 1995 Jul 18;92(15):7125–7129. doi: 10.1073/pnas.92.15.7125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  78. Wang J., Bell L. R. The Sex-lethal amino terminus mediates cooperative interactions in RNA binding and is essential for splicing regulation. Genes Dev. 1994 Sep 1;8(17):2072–2085. doi: 10.1101/gad.8.17.2072. [DOI] [PubMed] [Google Scholar]
  79. Wang J., Dong Z., Bell L. R. Sex-lethal interactions with protein and RNA. Roles of glycine-rich and RNA binding domains. J Biol Chem. 1997 Aug 29;272(35):22227–22235. doi: 10.1074/jbc.272.35.22227. [DOI] [PubMed] [Google Scholar]
  80. Winston R. L., Millar D. P., Gottesfeld J. M., Kent S. B. Characterization of the DNA binding properties of the bHLH domain of Deadpan to single and tandem sites. Biochemistry. 1999 Apr 20;38(16):5138–5146. doi: 10.1021/bi982856a. [DOI] [PubMed] [Google Scholar]
  81. Yang D., Lu H., Hong Y., Jinks T. M., Estes P. A., Erickson J. W. Interpretation of X chromosome dose at Sex-lethal requires non-E-box sites for the basic helix-loop-helix proteins SISB and daughterless. Mol Cell Biol. 2001 Mar;21(5):1581–1592. doi: 10.1128/MCB.21.5.1581-1592.2001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  82. Yanowitz J. L., Deshpande G., Calhoun G., Schedl P. D. An N-terminal truncation uncouples the sex-transforming and dosage compensation functions of sex-lethal. Mol Cell Biol. 1999 Apr;19(4):3018–3028. doi: 10.1128/mcb.19.4.3018. [DOI] [PMC free article] [PubMed] [Google Scholar]
  83. Younger-Shepherd S., Vaessin H., Bier E., Jan L. Y., Jan Y. N. deadpan, an essential pan-neural gene encoding an HLH protein, acts as a denominator in Drosophila sex determination. Cell. 1992 Sep 18;70(6):911–922. doi: 10.1016/0092-8674(92)90242-5. [DOI] [PubMed] [Google Scholar]
  84. Zlokarnik G., Negulescu P. A., Knapp T. E., Mere L., Burres N., Feng L., Whitney M., Roemer K., Tsien R. Y. Quantitation of transcription and clonal selection of single living cells with beta-lactamase as reporter. Science. 1998 Jan 2;279(5347):84–88. doi: 10.1126/science.279.5347.84. [DOI] [PubMed] [Google Scholar]

Articles from Genetics are provided here courtesy of Oxford University Press

RESOURCES