Reference Report

Reference
Citation	Kadener, S., Stoleru, D., McDonald, M., Nawathean, P., Rosbash, M. (2007). Clockwork Orange is a transcriptional repressor and a new Drosophila circadian pacemaker component. Genes Dev. 21(13): 1675--1686. (Export to RIS)
FlyBase ID	FBrf0200951
Publication Type	Research paper
PubMed ID	17578907
PubMed Abstract	Many organisms use circadian clocks to keep temporal order and anticipate daily environmental changes. In Drosophila, the master clock gene Clock promotes the transcription of several key target genes. Two of these gene products, PER and TIM, repress CLK-CYC-mediated transcription. To recognize additional direct CLK target genes, we designed a genome-wide approach and identified clockwork orange (cwo) as a new core clock component. cwo encodes a transcriptional repressor that synergizes with PER and inhibits CLK-mediated activation. Consistent with this function, the mRNA profiles of CLK direct target genes in cwo mutant flies manifest high trough values and low amplitude oscillations. Because behavioral rhythmicity fails to persist in constant darkness (DD) with little or no effect on average mRNA levels in flies lacking cwo, transcriptional oscillation amplitude appears to be linked to rhythmicity. Moreover, the mutant flies are long period, consistent with the late repression indicated by the RNA profiles. These findings suggest that CWO acts preferentially in the late night to help terminate CLK-CYC-mediated transcription of direct target genes including cwo itself. The presence of mammalian homologs with circadian expression features (Dec1 and Dec2) suggests that a similar feedback mechanism exists in mammalian clocks.
DOI	10.1101/gad.1552607
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Language of Publication	English
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Parent Publication
Publication Type	Journal
Abbreviation	Genes Dev.
Title	Genes & Development
Publication Year	1987-
ISBN/ISSN	0890-9369
Data from Reference
Alleles (9)
	Avic\GFP^Scer\UAS.cUa Clk^Jrk cwo^e04207 cwo^f05073 cwo^Scer\UAS.cKa per⁰¹ Scer\GAL4^cwo-NP7442 Scer\GAL4^tim.PE w^+mC
Constructs (3)
	P{GAL4-tim.E} P{UAS-cwo.K} P{UAS-GFP.U}
Genes (32)
	Avic\GFP cbt CG3348 CG3764 CG6231 CG6767 CG8008 CG13624 CG13868 CG15096 CG18135 CG32170 CG42675 Clk cry cwo E(spl)m3-HLH E(spl)mβ-HLH Gadd45 l(2)08717 l(2)k01209 Mmp1 Pdf Pdp1 per Picot Scer\GAL4 sug tim Tret1-1 vri w
Insertions (3)
	P{GawB}NP7442 PBac{RB}cwo^e04207 PBac{WH}cwo^f05073
Natural transposons (1)
	P-element