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. 1997 Jul;17(7):3687–3693. doi: 10.1128/mcb.17.7.3687

A circadian enhancer mediates PER-dependent mRNA cycling in Drosophila melanogaster.

H Hao 1, D L Allen 1, P E Hardin 1
PMCID: PMC232220  PMID: 9199302

Abstract

Genes expressed under circadian-clock control are found in organisms ranging from prokaryotes to humans. In Drosophila melanogaster, the period (per) gene, which is required for clock function, is transcribed in a circadian manner. We have identified a circadian transcriptional enhancer within a 69-bp DNA fragment upstream of the per gene. This enhancer drives high-amplitude mRNA cycling under light-dark-cycling or constant-dark conditions, and this activity is per protein (PER) dependent. An E-box sequence within this 69-bp fragment is necessary for high-level expression, but not for rhythmic expression, indicating that PER mediates circadian transcription through other sequences in this fragment.

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Selected References

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  1. Anderson S. L., Kay S. A. Functional dissection of circadian clock- and phytochrome-regulated transcription of the Arabidopsis CAB2 gene. Proc Natl Acad Sci U S A. 1995 Feb 28;92(5):1500–1504. doi: 10.1073/pnas.92.5.1500. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Anderson S. L., Teakle G. R., Martino-Catt S. J., Kay S. A. Circadian clock- and phytochrome-regulated transcription is conferred by a 78 bp cis-acting domain of the Arabidopsis CAB2 promoter. Plant J. 1994 Oct;6(4):457–470. doi: 10.1046/j.1365-313x.1994.6040457.x. [DOI] [PubMed] [Google Scholar]
  3. Aronson B. D., Johnson K. A., Loros J. J., Dunlap J. C. Negative feedback defining a circadian clock: autoregulation of the clock gene frequency. Science. 1994 Mar 18;263(5153):1578–1584. doi: 10.1126/science.8128244. [DOI] [PubMed] [Google Scholar]
  4. Arpaia G., Loros J. J., Dunlap J. C., Morelli G., Macino G. The interplay of light and the circadian clock. Independent dual regulation of clock-controlled gene ccg-2(eas). Plant Physiol. 1993 Aug;102(4):1299–1305. doi: 10.1104/pp.102.4.1299. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bell-Pedersen D., Dunlap J. C., Loros J. J. Distinct cis-acting elements mediate clock, light, and developmental regulation of the Neurospora crassa eas (ccg-2) gene. Mol Cell Biol. 1996 Feb;16(2):513–521. doi: 10.1128/mcb.16.2.513. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Carre I. A., Kay S. A. Multiple DNA-Protein Complexes at a Circadian-Regulated Promoter Element. Plant Cell. 1995 Dec;7(12):2039–2051. doi: 10.1105/tpc.7.12.2039. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Citri Y., Colot H. V., Jacquier A. C., Yu Q., Hall J. C., Baltimore D., Rosbash M. A family of unusually spliced biologically active transcripts encoded by a Drosophila clock gene. Nature. 1987 Mar 5;326(6108):42–47. doi: 10.1038/326042a0. [DOI] [PubMed] [Google Scholar]
  8. Crews S. T., Thomas J. B., Goodman C. S. The Drosophila single-minded gene encodes a nuclear protein with sequence similarity to the per gene product. Cell. 1988 Jan 15;52(1):143–151. doi: 10.1016/0092-8674(88)90538-7. [DOI] [PubMed] [Google Scholar]
  9. Curtin K. D., Huang Z. J., Rosbash M. Temporally regulated nuclear entry of the Drosophila period protein contributes to the circadian clock. Neuron. 1995 Feb;14(2):365–372. doi: 10.1016/0896-6273(95)90292-9. [DOI] [PubMed] [Google Scholar]
  10. Edery I., Zwiebel L. J., Dembinska M. E., Rosbash M. Temporal phosphorylation of the Drosophila period protein. Proc Natl Acad Sci U S A. 1994 Mar 15;91(6):2260–2264. doi: 10.1073/pnas.91.6.2260. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Eskin A. Identification and physiology of circadian pacemakers. Introduction. Fed Proc. 1979 Nov;38(12):2570–2572. [PubMed] [Google Scholar]
  12. Foulkes N. S., Duval G., Sassone-Corsi P. Adaptive inducibility of CREM as transcriptional memory of circadian rhythms. Nature. 1996 May 2;381(6577):83–85. doi: 10.1038/381083a0. [DOI] [PubMed] [Google Scholar]
  13. Frisch B., Hardin P. E., Hamblen-Coyle M. J., Rosbash M., Hall J. C. A promoterless period gene mediates behavioral rhythmicity and cyclical per expression in a restricted subset of the Drosophila nervous system. Neuron. 1994 Mar;12(3):555–570. doi: 10.1016/0896-6273(94)90212-7. [DOI] [PubMed] [Google Scholar]
  14. Garabedian M. J., Shepherd B. M., Wensink P. C. A tissue-specific transcription enhancer from the Drosophila yolk protein 1 gene. Cell. 1986 Jun 20;45(6):859–867. doi: 10.1016/0092-8674(86)90560-x. [DOI] [PubMed] [Google Scholar]
  15. Gekakis N., Saez L., Delahaye-Brown A. M., Myers M. P., Sehgal A., Young M. W., Weitz C. J. Isolation of timeless by PER protein interaction: defective interaction between timeless protein and long-period mutant PERL. Science. 1995 Nov 3;270(5237):811–815. doi: 10.1126/science.270.5237.811. [DOI] [PubMed] [Google Scholar]
  16. Ghosh D. TFD: the transcription factors database. Nucleic Acids Res. 1992 May 11;20 (Suppl):2091–2093. doi: 10.1093/nar/20.suppl.2091. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Ginty D. D., Kornhauser J. M., Thompson M. A., Bading H., Mayo K. E., Takahashi J. S., Greenberg M. E. Regulation of CREB phosphorylation in the suprachiasmatic nucleus by light and a circadian clock. Science. 1993 Apr 9;260(5105):238–241. doi: 10.1126/science.8097062. [DOI] [PubMed] [Google Scholar]
  18. Giuliano G., Hoffman N. E., Ko K., Scolnik P. A., Cashmore A. R. A light-entrained circadian clock controls transcription of several plant genes. EMBO J. 1988 Dec 1;7(12):3635–3642. doi: 10.1002/j.1460-2075.1988.tb03244.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Hall J. C. Tripping along the trail to the molecular mechanisms of biological clocks. Trends Neurosci. 1995 May;18(5):230–240. doi: 10.1016/0166-2236(95)93908-g. [DOI] [PubMed] [Google Scholar]
  20. Hardin P. E. Analysis of period mRNA cycling in Drosophila head and body tissues indicates that body oscillators behave differently from head oscillators. Mol Cell Biol. 1994 Nov;14(11):7211–7218. doi: 10.1128/mcb.14.11.7211. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Hardin P. E., Hall J. C., Rosbash M. Circadian oscillations in period gene mRNA levels are transcriptionally regulated. Proc Natl Acad Sci U S A. 1992 Dec 15;89(24):11711–11715. doi: 10.1073/pnas.89.24.11711. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Hardin P. E., Hall J. C., Rosbash M. Feedback of the Drosophila period gene product on circadian cycling of its messenger RNA levels. Nature. 1990 Feb 8;343(6258):536–540. doi: 10.1038/343536a0. [DOI] [PubMed] [Google Scholar]
  23. Hardin S. H., Jones L. B., Homayouni R., McCollum J. C. Octamer-primed cycle sequencing: design of an optimized primer library. Genome Res. 1996 Jun;6(6):545–550. doi: 10.1101/gr.6.6.545. [DOI] [PubMed] [Google Scholar]
  24. Huang Z. J., Edery I., Rosbash M. PAS is a dimerization domain common to Drosophila period and several transcription factors. Nature. 1993 Jul 15;364(6434):259–262. doi: 10.1038/364259a0. [DOI] [PubMed] [Google Scholar]
  25. Koumenis C., Tran Q., Eskin A. The use of a reversible transcription inhibitor, DRB, to investigate the involvement of specific proteins in the ocular circadian system of Aplysia. J Biol Rhythms. 1996 Mar;11(1):45–56. doi: 10.1177/074873049601100105. [DOI] [PubMed] [Google Scholar]
  26. Lauter F. R., Russo V. E., Yanofsky C. Developmental and light regulation of eas, the structural gene for the rodlet protein of Neurospora. Genes Dev. 1992 Dec;6(12A):2373–2381. doi: 10.1101/gad.6.12a.2373. [DOI] [PubMed] [Google Scholar]
  27. Lee C., Parikh V., Itsukaichi T., Bae K., Edery I. Resetting the Drosophila clock by photic regulation of PER and a PER-TIM complex. Science. 1996 Mar 22;271(5256):1740–1744. doi: 10.1126/science.271.5256.1740. [DOI] [PubMed] [Google Scholar]
  28. Liu X., Yu Q. A., Huang Z. S., Zwiebel L. J., Hall J. C., Rosbash M. The strength and periodicity of D. melanogaster circadian rhythms are differentially affected by alterations in period gene expression. Neuron. 1991 May;6(5):753–766. doi: 10.1016/0896-6273(91)90172-v. [DOI] [PubMed] [Google Scholar]
  29. Liu X., Zwiebel L. J., Hinton D., Benzer S., Hall J. C., Rosbash M. The period gene encodes a predominantly nuclear protein in adult Drosophila. J Neurosci. 1992 Jul;12(7):2735–2744. doi: 10.1523/JNEUROSCI.12-07-02735.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Loros J. J., Denome S. A., Dunlap J. C. Molecular cloning of genes under control of the circadian clock in Neurospora. Science. 1989 Jan 20;243(4889):385–388. doi: 10.1126/science.2563175. [DOI] [PubMed] [Google Scholar]
  31. Loros J. J., Dunlap J. C. Neurospora crassa clock-controlled genes are regulated at the level of transcription. Mol Cell Biol. 1991 Jan;11(1):558–563. doi: 10.1128/mcb.11.1.558. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Molina C. A., Foulkes N. S., Lalli E., Sassone-Corsi P. Inducibility and negative autoregulation of CREM: an alternative promoter directs the expression of ICER, an early response repressor. Cell. 1993 Dec 3;75(5):875–886. doi: 10.1016/0092-8674(93)90532-u. [DOI] [PubMed] [Google Scholar]
  33. Murre C., McCaw P. S., Baltimore D. A new DNA binding and dimerization motif in immunoglobulin enhancer binding, daughterless, MyoD, and myc proteins. Cell. 1989 Mar 10;56(5):777–783. doi: 10.1016/0092-8674(89)90682-x. [DOI] [PubMed] [Google Scholar]
  34. Myers M. P., Wager-Smith K., Wesley C. S., Young M. W., Sehgal A. Positional cloning and sequence analysis of the Drosophila clock gene, timeless. Science. 1995 Nov 3;270(5237):805–808. doi: 10.1126/science.270.5237.805. [DOI] [PubMed] [Google Scholar]
  35. O'Kane C. J., Gehring W. J. Detection in situ of genomic regulatory elements in Drosophila. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9123–9127. doi: 10.1073/pnas.84.24.9123. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Piechulla B., Gruissem W. Diurnal mRNA fluctuations of nuclear and plastid genes in developing tomato fruits. EMBO J. 1987 Dec 1;6(12):3593–3599. doi: 10.1002/j.1460-2075.1987.tb02690.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Pilgrim M. L., Caspar T., Quail P. H., McClung C. R. Circadian and light-regulated expression of nitrate reductase in Arabidopsis. Plant Mol Biol. 1993 Oct;23(2):349–364. doi: 10.1007/BF00029010. [DOI] [PubMed] [Google Scholar]
  38. Price J. L., Dembinska M. E., Young M. W., Rosbash M. Suppression of PERIOD protein abundance and circadian cycling by the Drosophila clock mutation timeless. EMBO J. 1995 Aug 15;14(16):4044–4049. doi: 10.1002/j.1460-2075.1995.tb00075.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Qiu J., Hardin P. E. per mRNA cycling is locked to lights-off under photoperiodic conditions that support circadian feedback loop function. Mol Cell Biol. 1996 Aug;16(8):4182–4188. doi: 10.1128/mcb.16.8.4182. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Raju U., Koumenis C., Nunez-Regueiro M., Eskin A. Alteration of the phase and period of a circadian oscillator by a reversible transcription inhibitor. Science. 1991 Aug 9;253(5020):673–675. doi: 10.1126/science.1871602. [DOI] [PubMed] [Google Scholar]
  41. Redinbaugh M. G., Sabre M., Scandalios J. G. Expression of the maize Cat3 catalase gene is under the influence of a circadian rhythm. Proc Natl Acad Sci U S A. 1990 Sep;87(17):6853–6857. doi: 10.1073/pnas.87.17.6853. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Rosbash M., Hall J. C. The molecular biology of circadian rhythms. Neuron. 1989 Oct;3(4):387–398. doi: 10.1016/0896-6273(89)90199-2. [DOI] [PubMed] [Google Scholar]
  43. Sauman I., Reppert S. M. Circadian clock neurons in the silkmoth Antheraea pernyi: novel mechanisms of Period protein regulation. Neuron. 1996 Nov;17(5):889–900. doi: 10.1016/s0896-6273(00)80220-2. [DOI] [PubMed] [Google Scholar]
  44. Sehgal A., Price J. L., Man B., Young M. W. Loss of circadian behavioral rhythms and per RNA oscillations in the Drosophila mutant timeless. Science. 1994 Mar 18;263(5153):1603–1606. doi: 10.1126/science.8128246. [DOI] [PubMed] [Google Scholar]
  45. Sehgal A., Rothenfluh-Hilfiker A., Hunter-Ensor M., Chen Y., Myers M. P., Young M. W. Rhythmic expression of timeless: a basis for promoting circadian cycles in period gene autoregulation. Science. 1995 Nov 3;270(5237):808–810. doi: 10.1126/science.270.5237.808. [DOI] [PubMed] [Google Scholar]
  46. Stehle J. H., Foulkes N. S., Molina C. A., Simonneaux V., Pévet P., Sassone-Corsi P. Adrenergic signals direct rhythmic expression of transcriptional repressor CREM in the pineal gland. Nature. 1993 Sep 23;365(6444):314–320. doi: 10.1038/365314a0. [DOI] [PubMed] [Google Scholar]
  47. Takahashi J. S. Circadian clock genes are ticking. Science. 1992 Oct 9;258(5080):238–240. doi: 10.1126/science.1384127. [DOI] [PubMed] [Google Scholar]
  48. Takahashi J. S. Circadian-clock regulation of gene expression. Curr Opin Genet Dev. 1993 Apr;3(2):301–309. doi: 10.1016/0959-437x(93)90038-q. [DOI] [PubMed] [Google Scholar]
  49. Van Gelder R. N., Bae H., Palazzolo M. J., Krasnow M. A. Extent and character of circadian gene expression in Drosophila melanogaster: identification of twenty oscillating mRNAs in the fly head. Curr Biol. 1995 Dec 1;5(12):1424–1436. doi: 10.1016/s0960-9822(95)00280-6. [DOI] [PubMed] [Google Scholar]
  50. Van Gelder R. N., Krasnow M. A. A novel circadianly expressed Drosophila melanogaster gene dependent on the period gene for its rhythmic expression. EMBO J. 1996 Apr 1;15(7):1625–1631. [PMC free article] [PubMed] [Google Scholar]
  51. Vosshall L. B., Price J. L., Sehgal A., Saez L., Young M. W. Block in nuclear localization of period protein by a second clock mutation, timeless. Science. 1994 Mar 18;263(5153):1606–1609. doi: 10.1126/science.8128247. [DOI] [PubMed] [Google Scholar]
  52. Wharton K. A., Jr, Crews S. T. CNS midline enhancers of the Drosophila slit and Toll genes. Mech Dev. 1993 Mar;40(3):141–154. doi: 10.1016/0925-4773(93)90072-6. [DOI] [PubMed] [Google Scholar]
  53. Zeng H., Hardin P. E., Rosbash M. Constitutive overexpression of the Drosophila period protein inhibits period mRNA cycling. EMBO J. 1994 Aug 1;13(15):3590–3598. doi: 10.1002/j.1460-2075.1994.tb06666.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Zeng H., Qian Z., Myers M. P., Rosbash M. A light-entrainment mechanism for the Drosophila circadian clock. Nature. 1996 Mar 14;380(6570):129–135. doi: 10.1038/380129a0. [DOI] [PubMed] [Google Scholar]
  55. Zerr D. M., Hall J. C., Rosbash M., Siwicki K. K. Circadian fluctuations of period protein immunoreactivity in the CNS and the visual system of Drosophila. J Neurosci. 1990 Aug;10(8):2749–2762. doi: 10.1523/JNEUROSCI.10-08-02749.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Zwiebel L. J., Hardin P. E., Liu X., Hall J. C., Rosbash M. A post-transcriptional mechanism contributes to circadian cycling of a per-beta-galactosidase fusion protein. Proc Natl Acad Sci U S A. 1991 May 1;88(9):3882–3886. doi: 10.1073/pnas.88.9.3882. [DOI] [PMC free article] [PubMed] [Google Scholar]

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