Clockwork orange encodes a transcriptional repressor important for circadian-clock amplitude in Drosophila

Curr Biol. 2007 Jun 19;17(12):1082-9. doi: 10.1016/j.cub.2007.05.039. Epub 2007 Jun 7.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Clocks
  • Circadian Rhythm / genetics
  • Circadian Rhythm / physiology*
  • Drosophila / genetics
  • Drosophila / metabolism
  • Drosophila / physiology*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Gene Expression Regulation*
  • Mutation
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Transcription, Genetic

Substances

  • Cwo protein, Drosophila
  • Drosophila Proteins
  • Repressor Proteins