Dynamic PER repression mechanisms in the Drosophila circadian clock: from on-DNA to off-DNA.

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, approximately 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.
Mesh Terms:
Animals, CLOCK Proteins, Cells, Cultured, Circadian Rhythm, DNA, DNA Polymerase II, Drosophila Proteins, Drosophila melanogaster, Gene Expression Regulation, Period Circadian Proteins, Promoter Regions, Genetic, Protein Binding
Genes Dev.
Date: Feb. 15, 2010
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