title: Clockwork orange encodes a transcriptional repressor important for circadian-clock amplitude in Drosophila.
abstract: 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. Microarray studies have identified numerous rhythmically expressed transcripts, some of which are potential direct CLK targets. 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.
authors.affiliation: Department of Neurobiology and Physiology, Northwestern University, Evanston, Illinois 60208, USA.
authors.forename: Chunghun
authors.initials: C
authors.lastname: Lim
authors.forename: Brian Y
authors.initials: BY
authors.lastname: Chung
authors.forename: Jena L
authors.initials: JL
authors.lastname: Pitman
authors.forename: Jermaine J
authors.initials: JJ
authors.lastname: McGill
authors.forename: Suraj
authors.initials: S
authors.lastname: Pradhan
authors.forename: Jongbin
authors.initials: J
authors.lastname: Lee
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Keegan
authors.forename: Joonho
authors.initials: J
authors.lastname: Choe
authors.forename: Ravi
authors.initials: R
authors.lastname: Allada
mesh_terms: D000818:Animals; D001683:Biological Clocks; D002940:Circadian Rhythm / Q000235:genetics / Q000502:physiology*; D004330:Drosophila / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D009154:Mutation; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: C521952:Cwo protein, Drosophila; D029721:Drosophila Proteins; D012097:Repressor Proteins