Activating inhibitors and inhibiting activators: A day in the life of a fly

Current Opinion in Neurobiology

Volumn 8, Issue 5, 1998, Pages 642-647

  Hardin, Paul E ^a  

^a University of Houston   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CIRCADIAN RHYTHM; DROSOPHILA MELANOGASTER; FEEDBACK SYSTEM; GENE EXPRESSION; GENETIC TRANSCRIPTION; NONHUMAN; OSCILLATOR; PRIORITY JOURNAL; REVIEW;

DROSOPHILA MELANOGASTER;

EID: 0032191089     PISSN: 09594388     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0959-4388(98)80093-7     Document Type: Article

References (46)

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9. of outstanding interest Darlington TK, Wager-Smith K, Ceriani MF, Staknis D, Gekakis N, Steeves TDL, Weitz CJ, Takahashi JS, Kay SA. Closing the circadian feedback loop: CLOCK induced transcription of its own inhibitors, period and timeless. Science. 280:1998;1599-1603 A major paper that first describes the cloning of a Drosophila Clock homolog (dClk), and then shows that dCLK protein dimerizes with Drosophila BMAL1 protein to activate E-box-dependent transcription (using the per E-box and an E-box upstream of tim) in cultured Drosophila S2 cells. Evidence that PER and TIM act to repress dCLK/dBMAL1 transcription from the per E-box in S2 cells is also presented, indicating that repression is controlled by these E-box-binding factors.
10. of outstanding interest Rutila JE, Suri V, Le M, So WV, Rosbash M, Hall JC. CYCLE is a second bHLH-PAS clock protein essential for circadian rhythmicity and transcription of Drosophila period and timeless. Cell. 93:1998;805-814 This is the first paper to show that dCLK's binding partner - termed CYCLE (CYC) in Drosophila as opposed to dBMAL1 in mammals - functions within the circadian oscillator in vivo. A cyc mutant that removes the carboxy-terminal 60% of the protein is found to be behaviorally arrhythmic as a result of its inability to activate per and tim transcription.
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38. of special interest Stanewsky R, Frisch B, Brandes C, Hamblen-Coyle MJ, Rosbash M, Hall JC. Temporal and spatial expression patterns of transgenes containing increasing amounts of the Drosophila clock gene period and a lacZ reporter: mapping elements of the PER protein involved in circadian cycling. J Neurosci. 17:1997;676-696 An important study that used PER - β-galactosidase fusion proteins containing varying lengths of PER to show that PER cycling is mediated by sequences between residues 637 and 868 and that behavioral rescue requires almost the entire PER sequence.
39. of special interest Dembinska ME, Stanewsky R, Hall JC, Rosbash M. Circadian cycling of a period-lacZ fusion protein in Drosophila: evidence for cyclical degradation. J Biol Rhythms. 12:1997;157-172 This paper also used PER - β-galactosidase fusion proteins containing varying lengths of PER to show that a destabilizing sequence resides between residues 637 and 868 (see [38]). Along with [38], this study shows that PER cycling is controlled post-transcriptionally through the degradation of PER.
40. of special interest Stanewsky R, Jamison CF, Plautz JD, Kay SA, Hall JC. Multiple circadian-regulated elements contribute to cycling period gene expression in Drosophila. EMBO J. 16:1997;5006-5018 This paper used per promoter driven luciferase reporter genes to show that per mRNA cycling is under some degree of post-transcriptional control.
41. of special interest Hao H, Allen DL, Hardin PE. A circadian enhancer mediates PER-dependent mRNA cycling in Drosophila. Mol Cell Biol. 17:1997;3687-3693 This study characterized a regulatory sequence responsible for circadian transcription of per. An E-box within this 69 bp circadian regulatory sequence is required for high level expression and is a target for bHLH - PAS transcriptional activators, suggesting a model in which PER represses transcription by disrupting bHLH - PAS activators.
42. of special interest King DP, Zhao Y, Sangoram AM, Wilsbacher LD, Tanaka M, Antoch MP, Steeves TDL, Vitaterna MH, Kornhauser JM, Lowrey PL, et al. Positional cloning of the mouse circadian Clock gene. Cell. 89:1997;641-653 A major paper describing the molecular characterization of CLOCK, a bHLH - PAS protein that, in mutant form, disrupts activity rhythms in mice. This work provides a link between Drosophila (which have an E-box target) and mammals (which have a putative E-box-binding factor).
43. of outstanding interest Gekakis N, Staknis D, Nguyen HB, Davis FC, Wilsbacher LD, King DP, Takahashi JS, Weitz CJ. Role of the CLOCK protein in the mammalian circadian mechanism. Science. 280:1998;1564-1569 This study shows that CLOCK dimerizes with BMAL1 to activate transcription from E-box sequences. Once BMAL1 was identified as a CLOCK-binding partner, yeast one-hybrid studies were used to show that CLOCK - BMAL1 dimers activate transcription from the Drosophila E-box sequence and similar E-box sequences were discovered upstream of the mper1 gene.
44. of outstanding interest Hogenesch JB, Gu Y-Z, Jain S, Bradfield CA. The basic-helix-loop-helix-PAS orphan MOP3 forms transcriptionally active complexes with circadian and hypoxia factors. Proc Natl Acad Sci USA. 95:1998;5474-5479 This work used yeast two-hybrid technique to show that MOP3, which is equivalent to BMAL1, dimerizes strongly with CLOCK. These MOP3 - CLOCK dimers are capable of activating transcription by directly binding to E-boxes similar to that which upstream of Drosophila per.
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46. of special interest Cheng Y, Hardin PE. Drosophila photoreceptors contain an autonomous circadian oscillator that can function without period mRNA cycling. J Neurosci. 18:1998;741-750 This paper shows that per mRNA cycling in not required for circadian feedback loop function because constant levels of per mRNA give rise to cycling PER levels in constant dark conditions. This result suggests that either other cycling mRNAs (such as tim and perhaps dClk) or post-transcriptional regulatory events are sufficient to maintain feedback loop function.