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Closing the Circadian Loop: CLOCK-Induced Transcription of Its Own Inhibitors per and tim
Abstract
The circadian oscillator generates a rhythmic output with a period of about 24 hours. Despite extensive studies in several model systems, the biochemical mode of action has not yet been demonstrated for any of its components. Here, the Drosophila CLOCK protein was shown to induce transcription of the circadian rhythm genes period and timeless . dCLOCK functioned as a heterodimer with a Drosophila homolog of BMAL1. These proteins acted through an E-box sequence in the period promoter. The timeless promoter contains an 18–base pair element encompassing an E-box, which was sufficient to confer dCLOCK responsiveness to a reporter gene. PERIOD and TIMELESS proteins blocked dCLOCK's ability to transactivate their promoters via the E-box. Thus, dCLOCK drives expression of period and timeless, which in turn inhibit dCLOCK's activity and close the circadian loop.
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Citations
Cited by
Molecular Bases for Circadian Clocks
Dunlap, J. C. (1999) · Cell · doi:10.1016/s0092-8674(00)80566-8 · Cited by 2,900
Stability, precision, and near-24-hour period of the human circadian pacemaker
Czeisler, C. A., Duffy, J. F., Shanahan, T. L., Brown, E. N., Mitchell, J. F., Rimmer, D. W., Ronda, J. M., Silva, E. J., Allan, J. S., Emens, J. S., et al. (1999) · Science · doi:10.1126/science.284.5423.2177 · Cited by 1,705
Mop3 is an essential component of the master circadian pacemaker in mammals.
Bunger, M. K., Wilsbacher, L. D., Moran, S. M., Clendenin, C., Radcliffe, L. A., Hogenesch, J. B., Simon, M. C., Takahashi, J. S., & Bradfield, C. A. (2000) · Cell · doi:10.1016/s0092-8674(00)00205-1 · Cited by 1,621
Self-citationPAS Domains: Internal Sensors of Oxygen, Redox Potential, and Light
Taylor, B. L., & Zhulin, I. B. (1999) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.63.2.479-506.1999 · Cited by 1,632
mCRY1 and mCRY2 are essential components of the negative limb of the circadian clock feedback loop
Kume, K., Zylka, M. J., Sriram, S., Shearman, L. P., Weaver, D. R., Jin, X., Maywood, E. S., Hastings, M. H., & Reppert, S. M. (1999) · Cell · doi:10.1016/s0092-8674(00)81014-4 · Cited by 1,617
Metadata
- Authors
- Darlington, T. K., Wager-Smith, K., Ceriani, M. F., Staknis, D., Gekakis, N., Steeves, T. D. L., Weitz, C. J., Takahashi, J. S., & Kay, S. A.
- Venue
- Science
- Published
- 1998-06-05
- Volume
- 280
- Issue
- 5369
- Pages
- 1599-1603
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2065793682
- Cited by
- 825
- References
- 0
- FWCI
- 25.03
- Type
- journal article
- Language
- en
- Open access
- closed
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- Darlington, T. K., Wager-Smith, K., Ceriani, M. F., Staknis, D., Gekakis, N., Steeves, T. D. L., Weitz, C. J., Takahashi, J. S., & Kay, S. A. (1998). Closing the Circadian Loop: CLOCK-Induced Transcription of Its Own Inhibitors per and tim. Science. https://doi.org/10.1126/science.280.5369.1599
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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