Constructing a feedback loop with circadian clock molecules from the silkmoth, Antheraea pernyi
Authors
Chang, Dennis C.McWatters, Harriet G.
Williams, Julie A.
Gotter, Anthony L.
Levine, Joel D.
Reppert, Steven M.
Student Authors
Dennis C. ChangDocument Type
Journal ArticlePublication Date
2003-10-03Keywords
ARNTL Transcription FactorsAmino Acid Sequence
Animals
Base Sequence
Basic Helix-Loop-Helix Transcription Factors
CLOCK Proteins
Cell Line
*Circadian Rhythm
Cloning, Molecular
Drosophila
Drosophila Proteins
Evolution, Molecular
Feedback, Physiological
Immunohistochemistry
Insects
Luciferases
Models, Genetic
Molecular Sequence Data
Moths
Mutagenesis, Site-Directed
Nuclear Proteins
Period Circadian Proteins
Plasmids
Protein Structure, Tertiary
Sequence Homology, Amino Acid
Trans-Activators
*Transcription, Genetic
Transcriptional Activation
Transfection
Neuroscience and Neurobiology
Metadata
Show full item recordAbstract
Circadian clocks are important regulators of behavior and physiology. The circadian clock of Drosophila depends on an autoinhibitory feedback loop involving dCLOCK, CYCLE (also called dBMAL, for Drosophila brain and muscle ARNT-like protein), dPERIOD, and dTIMELESS. Recent studies suggest that the clock mechanism in other insect species may differ strikingly from that of Drosophila. We cloned Clock, Bmal, and Timeless homologs (apClock, apBmal, and apTimeless) from the silkmoth Antheraea pernyi, from which a Period homolog (apPeriod) has already been cloned. In Schneider 2 (S2) cell culture assays, apCLOCK:apBMAL activates transcription through an E-box enhancer element found in the 5' region of the apPeriod gene. Furthermore, apPERIOD can robustly inhibit apCLOCK: apBMAL-mediated transactivation, and apTIMELESS can augment this inhibition. Thus, a complete feedback loop, resembling that found in Drosophila, can be constructed from silkmoth CLOCK, BMAL, PERIOD, and TIMELESS. Our results suggest that the circadian autoinhibitory feedback loop discovered in Drosophila is likely to be widespread among insects. However, whereas the transactivation domain in Drosophila lies in the C terminus of dCLOCK, in A. pernyi, it lies in the C terminus of apBMAL, which is highly conserved with the C termini of BMALs in other insects (except Drosophila) and in vertebrates. Our analysis sheds light on the molecular function and evolution of clock genes in the animal kingdom.Source
J Biol Chem. 2003 Oct 3;278(40):38149-58. Epub 2003 Jul 17. Link to article on publisher's siteDOI
10.1074/jbc.M306937200Permanent Link to this Item
http://hdl.handle.net/20.500.14038/38048PubMed ID
12869551Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1074/jbc.M306937200
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