VRILLE Feeds Back to Control Circadian Transcription of Clock in the Drosophila Circadian Oscillator

• Published in: Neuron (Cambridge, Mass.) Vol. 37; no. 2; pp. 249 - 261
• Main Authors: Glossop, Nicholas R.J., Houl, Jerry H., Zheng, Hao, Ng, Fanny S., Dudek, Scott M., Hardin, Paul E.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 23.01.2003; Elsevier Limited
• Subjects: Animals; Animals, Genetically Modified; Binding Sites; Blotting, Western; Circadian rhythm; Circadian Rhythm - genetics; CLOCK Proteins; DNA-Binding Proteins - biosynthesis; DNA-Binding Proteins - metabolism; Drosophila - physiology; Drosophila Proteins; Electrophoretic Mobility Shift Assay; Feedback; Feedback - physiology; G-Box Binding Factors; Gene expression; Hot Temperature; Immunohistochemistry; Insects; Molecular Sequence Data; Nuclease Protection Assays; Photoreceptor Cells, Invertebrate - physiology; Proteins; RNA polymerase; RNA, Messenger - biosynthesis; Trans-Activators - genetics; Transcription Factors - biosynthesis; Transcription Factors - genetics; Transcription Factors - metabolism; Transcription Factors - physiology
• ISSN: 0896-6273; 1097-4199
• 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.