PMID:17578908

Citation	Matsumoto, A, Ukai-Tadenuma, M, Yamada, RG, Houl, J, Uno, KD, Kasukawa, T, Dauwalder, B, Itoh, TQ, Takahashi, K, Ueda, R, Hardin, PE, Tanimura, T and Ueda, HR (2007) A functional genomics strategy reveals clockwork orange as a transcriptional regulator in the Drosophila circadian clock. Genes Dev. 21:1687-700
Abstract	The Drosophila circadian clock consists of integrated autoregulatory feedback loops, making the clock difficult to elucidate without comprehensively identifying the network components in vivo. Previous studies have adopted genome-wide screening for clock-controlled genes using high-density oligonucleotide arrays that identified hundreds of clock-controlled genes. In an attempt to identify the core clock genes among these candidates, we applied genome-wide functional screening using an RNA interference (RNAi) system in vivo. Here we report the identification of novel clock gene candidates including clockwork orange (cwo), a transcriptional repressor belonging to the basic helix-loop-helix ORANGE family. cwo is rhythmically expressed and directly regulated by CLK-CYC through canonical E-box sequences. A genome-wide search for its target genes using the Drosophila genome tiling array revealed that cwo forms its own negative feedback loop and directly suppresses the expression of other clock genes through the E-box sequence. Furthermore, this negative transcriptional feedback loop contributes to sustaining a high-amplitude circadian oscillation in vivo. Based on these results, we propose that the competition between cyclic CLK-CYC activity and the adjustable threshold imposed by CWO keeps E-box-mediated transcription within the controllable range of its activity, thereby rendering a Drosophila circadian clock capable of generating high-amplitude oscillation.
Links	PubMed PMC1899476 Online version:10.1101/gad.1552207
Keywords	Amino Acid Sequence; Animals; Animals, Genetically Modified; Base Sequence; Basic Helix-Loop-Helix Transcription Factors/genetics; Basic Helix-Loop-Helix Transcription Factors/metabolism; Biological Clocks/genetics; CLOCK Proteins; Cells, Cultured; Circadian Rhythm/genetics; Drosophila Proteins/genetics; Drosophila Proteins/physiology; Drosophila melanogaster/genetics; Drosophila melanogaster/physiology; E-Box Elements; Gene Expression Regulation; Genome, Insect; Genomics; Models, Biological; Molecular Sequence Data; Neurons/metabolism; Repressor Proteins/genetics; Repressor Proteins/physiology; Sequence Homology, Amino Acid; Transcription Factors/physiology; Transcription, Genetic
edit table

Annotations

Gene product	Qualifier	GO ID	GO term name	Evidence Code	with/from	Aspect	Notes	Status
edit table

References

See Help:References for how to manage references in GONUTS.