Dynamic PER repression mechanisms in the <i>Drosophila</i> circadian clock: from on-DNA to off-DNA

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<jats:p>Transcriptional feedback loops are central to the generation and maintenance of circadian rhythms. In animal systems as well as <jats:italic>Neurospora</jats:italic>, transcriptional repression is believed to occur by catalytic post-translational events. We report here in the <jats:italic>Drosophila</jats:italic> 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.</jats:p>

Journal

  • Genes & Development

    Genes & Development 24 (4), 358-367, 2010-02-15

    Cold Spring Harbor Laboratory

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