VRILLE feeds back to control circadian transcription of Clock in the Drosophila circadian oscillator

Neuron. 2003 Jan 23;37(2):249-61. doi: 10.1016/s0896-6273(03)00002-3.


The Drosophila circadian oscillator consists of interlocked period (per)/timeless (tim) and Clock (Clk) transcriptional/translational feedback loops. Within these feedback loops, CLK and CYCLE (CYC) activate per and tim transcription at the same time as they repress Clk transcription, thus controlling the opposite cycling phases of these transcripts. CLK-CYC directly bind E box elements to activate transcription, but the mechanism of CLK-CYC-dependent repression is not known. Here we show that a CLK-CYC-activated gene, vrille (vri), encodes a repressor of Clk transcription, thereby identifying vri as a key negative component of the Clk feedback loop in Drosophila's circadian oscillator. The blue light photoreceptor encoding cryptochrome (cry) gene is also a target for VRI repression, suggesting a broader role for VRI in the rhythmic repression of output genes that cycle in phase with Clk.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Binding Sites
  • Blotting, Western
  • CLOCK Proteins
  • Circadian Rhythm / genetics*
  • DNA-Binding Proteins / biosynthesis
  • DNA-Binding Proteins / metabolism
  • Drosophila / physiology*
  • Drosophila Proteins*
  • Electrophoretic Mobility Shift Assay
  • Feedback / physiology
  • G-Box Binding Factors
  • Hot Temperature
  • Immunohistochemistry
  • Molecular Sequence Data
  • Nuclease Protection Assays
  • Photoreceptor Cells, Invertebrate / physiology
  • RNA, Messenger / biosynthesis
  • Trans-Activators / genetics*
  • Transcription Factors / biosynthesis
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Transcription Factors / physiology*


  • DNA-Binding Proteins
  • Drosophila Proteins
  • G-Box Binding Factors
  • RNA, Messenger
  • Trans-Activators
  • Transcription Factors
  • vri protein, Drosophila
  • CLOCK Proteins

Associated data

  • GENBANK/AI404327