clockwork orange Encodes a Transcriptional Repressor Important for Circadian-Clock Amplitude in Drosophila

Chunghun Lim, Brian Y. Chung, Jena L. Pitman, Jermaine J. McGill, Suraj Pradhan, Jongbin Lee, Kevin P. Keegan, Joonho Choe*, Ravi Allada

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

124 Scopus citations


Gene transcription is a central timekeeping process in animal clocks. In Drosophila, the basic helix-loop helix (bHLH)-PAS transcription-factor heterodimer, CLOCK/CYCLE (CLK/CYC), transcriptionally activates the clock components period (per), timeless (tim), Par domain protein 1 (Pdp1), and vrille (vri), which feed back and regulate distinct features of CLK/CYC function [1]. Microarray studies have identified numerous rhythmically expressed transcripts [2-7], some of which are potential direct CLK targets [7]. Here we demonstrate a circadian function for one such target, a bHLH-Orange repressor, CG17100/CLOCKWORK ORANGE (CWO). cwo is rhythmically expressed, and levels are reduced in Clk mutants, suggesting that cwo is CLK activated in vivo. cwo mutants display reduced-amplitude molecular and behavioral rhythms with lengthened periods. Molecular analysis suggests that CWO acts, in part, by repressing CLK target genes. We propose that CWO acts as a transcriptional and behavioral rhythm amplifier.

Original languageEnglish (US)
Pages (from-to)1082-1089
Number of pages8
JournalCurrent Biology
Issue number12
StatePublished - Jun 19 2007



ASJC Scopus subject areas

  • General Agricultural and Biological Sciences
  • General Biochemistry, Genetics and Molecular Biology


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