Modeling circadian oscillations with interlocking positive and negative feedback loops.

摘要: Both positive and negative feedback loops of transcriptional regulation have been proposed to be important for the generation circadian rhythms. To test sufficiency mechanisms, two differential equation-based models were constructed describe Neurospora crassa Drosophila melanogaster oscillators. In model oscillator, FRQ suppresses frq transcription by binding a complex activators WC-1 WC-2, thus yielding feedback. also activates synthesis WC-1, which in turn transcription, PER TIM are represented “lumped” variable, “PER.” its own regulator dCLOCK, binds dCLOCK de-repress dclock , per displayed oscillations that robust parameter variations noise entrained simulated light/dark cycles. Circadian only obtained if time delays included represent processes not modeled detail (e.g., translation). both models, preserved when was removed.