PER-dependent rhythms in CLK phosphorylation and E-box binding regulate circadian transcription
Open Access
- 15 March 2006
- journal article
- Published by Cold Spring Harbor Laboratory in Genes & Development
- Vol. 20 (6), 723-733
- https://doi.org/10.1101/gad.1404406
Abstract
Transcriptional activation by CLOCK-CYCLE (CLK-CYC) heterodimers and repression by PERIOD-TIMELESS (PER-TIM) heterodimers are essential for circadian oscillator function in Drosophila. PER-TIM was previously found to interact with CLK-CYC to repress transcription, and here we show that this interaction inhibits binding of CLK-CYC to E-box regulatory elements in vivo. Coincident with the interaction between PER-TIM and CLK-CYC is the hyperphosphorylation of CLK. This hyperphosphorylation occurs in parallel with the PER-dependent entry of DOUBLE-TIME (DBT) kinase into a complex with CLK-CYC, where DBT destabilizes both CLK and PER. Once PER and CLK are degraded, a novel hypophosphorylated form of CLK accumulates in parallel with E-box binding and transcriptional activation. These studies suggest that PER-dependent rhythms in CLK phosphorylation control rhythms in E-box-dependent transcription and CLK stability, thus linking PER and CLK function during the circadian cycle and distinguishing the transcriptional feedback mechanism in flies from that in mammals.Keywords
This publication has 53 references indexed in Scilit:
- Drosophila CLOCK Is Constitutively Expressed in Circadian Oscillator and Non-Oscillator CellsJournal of Biological Rhythms, 2006
- Transcriptional Feedback of Neurospora Circadian Clock Gene by Phosphorylation-Dependent Inactivation of Its Transcription FactorCell, 2005
- Posttranslational Mechanisms Regulate the Mammalian Circadian ClockCell, 2001
- Regulation of the cycling of timeless (tim) RNAJournal of Neurobiology, 2001
- The period E-box Is Sufficient to Drive Circadian Oscillation of Transcription In VivoJournal of Biological Rhythms, 2000
- Post-transcriptional regulation contributes to Drosophila clock gene mRNA cyclingThe EMBO Journal, 1997
- Sex-Specific Assembly of a Dosage Compensation Complex on the Nematode X ChromosomeScience, 1996
- Resetting the Drosophila Clock by Photic Regulation of PER and a PER-TIM ComplexScience, 1996
- Regulation of the Drosophila Protein Timeless Suggests a Mechanism for Resetting the Circadian Clock by LightCell, 1996
- Feedback of the Drosophila period gene product on circadian cycling of its messenger RNA levelsNature, 1990