Dynamic PER repression mechanisms in the Drosophila circadian clock: from on-DNA to off-DNA
- 15 February 2010
- journal article
- Published by Cold Spring Harbor Laboratory in Genes & Development
- Vol. 24 (4), 358-367
- https://doi.org/10.1101/gad.1883910
Abstract
Transcriptional feedback loops are central to the generation and maintenance of circadian rhythms. In animal systems as well as Neurospora, transcriptional repression is believed to occur by catalytic post-translational events. We report here in the Drosophila model two different mechanisms by which the circadian repressor PERIOD (PER) inhibits CLOCK/CYCLE (CLK/CYC)-mediated transcription. First, PER is recruited to circadian promoters, which leads to the nighttime decrease of CLK/CYC activity. This decrease is proportional to PER levels on DNA, and PER recruitment probably occurs via CLK. Then CLK is released from DNA and sequestered in a strong, ∼1:1 PER–CLK off-DNA complex. The data indicate that the PER levels bound to CLK change dynamically and are important for repression, first on-DNA and then off-DNA. They also suggest that these mechanisms occur upstream of post-translational events, and that elements of this two-step mechanism likely apply to mammals.Keywords
This publication has 35 references indexed in Scilit:
- Rhythmic PER Abundance Defines a Critical Nodal Point for Negative Feedback within the Circadian Clock MechanismMolecular Cell, 2009
- Nucleocytoplasmic shuttling and phosphorylation of BMAL1 are regulated by circadian clock in cultured fibroblastsGenes to Cells, 2003
- BMAL1-dependent circadian oscillation of nuclear CLOCK: posttranslational events induced by dimerization of transcriptional activators of the mammalian clock systemGenes & Development, 2003
- A clockwork web: circadian timing in brain and periphery, in health and diseaseNature Reviews Neuroscience, 2003
- Sequential Nuclear Accumulation of the Clock Proteins Period and Timeless in the Pacemaker Neurons ofDrosophila melanogasterJournal of Neuroscience, 2002
- Stopping Time: The Genetics of Fly and Mouse Circadian ClocksAnnual Review of Neuroscience, 2001
- Transcription activation by catabolite activator protein (CAP)Journal of Molecular Biology, 1999
- Post-transcriptional regulation contributes to Drosophila clock gene mRNA cyclingThe EMBO Journal, 1997
- Circadian Cycling of a PERIOD-β-galactosidase Fusion Protein in Drosophila: Evidence for Cyclical DegradationJournal of Biological Rhythms, 1997
- A light-entrainment mechanism for the Drosophila circadian clockNature, 1996