Drosophila CRYPTOCHROME is a circadian transcriptional repressor

Curr Biol. 2006 Mar 7;16(5):441-9. doi: 10.1016/j.cub.2006.01.034.


Background: Although most circadian clock components are conserved between Drosophila and mammals, the roles assigned to the CRYPTOCHROME (CRY) proteins are very different: Drosophila CRY functions as a circadian photoreceptor, whereas mammalian CRY proteins (mCRY1 and 2) are transcriptional repressors essential for molecular clock oscillations.

Results: Here we demonstrate that Drosophila CRY also functions as a transcriptional repressor. We found that RNA levels of genes directly activated by the transcription factors CLOCK (CLK) and CYCLE (CYC) are derepressed in cry(b) mutant eyes. Conversely, while overexpression of CRY and PERIOD (PER) in the eye repressed CLK/CYC activity, neither PER nor CRY repressed individually. Drosophila CRY also repressed CLK/CYC activity in cell culture. Repression by CRY appears confined to peripheral clocks, since neither cry(b) mutants nor overexpression of PER and CRY together in pacemaker neurons significantly affected molecular or behavioral rhythms. Increasing CLK/CYC activity by removing two repressors, PER and CRY, led to ectopic expression of the timeless clock gene, similar to overexpression of Clk itself.

Conclusions: Drosophila CRY functions as a transcriptional repressor required for the oscillation of peripheral circadian clocks and for the correct specification of clock cells.

Publication types

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

MeSH terms

  • ARNTL Transcription Factors
  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • CLOCK Proteins
  • Cells, Cultured
  • Circadian Rhythm / genetics*
  • Cryptochromes
  • Drosophila / cytology
  • Drosophila / genetics*
  • Drosophila / metabolism
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Drosophila Proteins / physiology*
  • Eye Proteins / physiology*
  • Gene Expression Regulation*
  • Nerve Net / metabolism
  • Neurons / metabolism
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Period Circadian Proteins
  • Photoreceptor Cells, Invertebrate / physiology*
  • RNA, Messenger / metabolism
  • Receptors, G-Protein-Coupled
  • Repressor Proteins / physiology*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism


  • ARNTL Transcription Factors
  • Basic Helix-Loop-Helix Transcription Factors
  • Clk protein, Drosophila
  • Cryptochromes
  • Drosophila Proteins
  • Eye Proteins
  • Nuclear Proteins
  • PER protein, Drosophila
  • Period Circadian Proteins
  • RNA, Messenger
  • Receptors, G-Protein-Coupled
  • Repressor Proteins
  • Transcription Factors
  • cry protein, Drosophila
  • cyc protein, Drosophila
  • tim protein, Drosophila
  • CLOCK Proteins