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Citation
Yu, W., Zheng, H., Houl, J.H., Dauwalder, B., Hardin, P.E. (2006). PER-dependent rhythms in CLK phosphorylation and E-box binding regulate circadian transcription.  Genes Dev. 20(6): 723--733.
FlyBase ID
FBrf0190570
Publication Type
Research paper
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.

PubMed ID
PubMed Central ID
PMC1434787 (PMC) (EuropePMC)
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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Genes Dev.
    Title
    Genes & Development
    Publication Year
    1987-
    ISBN/ISSN
    0890-9369
    Data From Reference
    Alleles (5)
    Genes (6)