title: Drosophila CRYPTOCHROME is a circadian transcriptional repressor.
abstract: 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.
authors.affiliation: Department of Biology, New York University, 100 Washington Square East, New York, New York 10003, USA.
authors.forename: Ben
authors.initials: B
authors.lastname: Collins
authors.forename: Esteban O
authors.initials: EO
authors.lastname: Mazzoni
authors.forename: Ralf
authors.initials: R
authors.lastname: Stanewsky
authors.forename: Justin
authors.initials: J
authors.lastname: Blau
mesh_terms: D056930:ARNTL Transcription Factors; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D056926:CLOCK Proteins; D002478:Cells, Cultured; D002940:Circadian Rhythm / Q000235:genetics*; D056931:Cryptochromes; D004330:Drosophila / Q000166:cytology / Q000235:genetics* / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D005136:Eye Proteins / Q000502:physiology*; D005786:Gene Expression Regulation; D009415:Nerve Net / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D056950:Period Circadian Proteins; D017956:Photoreceptor Cells, Invertebrate / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled; D012097:Repressor Proteins / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D056930:ARNTL Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins; D056926:CLOCK Proteins; D056931:Cryptochromes; D029721:Drosophila Proteins; D005136:Eye Proteins; D009687:Nuclear Proteins; D056950:Period Circadian Proteins; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D012097:Repressor Proteins; D014157:Transcription Factors; C120526:Clk protein, Drosophila; C539040:PER protein, Drosophila; C119828:cry protein, Drosophila; C112805:cyc protein, Drosophila; C096445:tim protein, Drosophila