Tuning the Mammalian Circadian Clock: Robust Synergy of Two Loops
Figure 6
Increase in transcription in elements of both RBR and PC loops can destroy the circadian oscillator.
(A–D) After a transient period of about 20 days we plotted the expression patterns for each of the four genes indicated. Skipping the transient region allows an enhancement of the effects on the system: damped oscillations give rise to flat expression profiles and small phase differences became better visible. Expression profiles for the indicated RNA are shown given different values of the respective RNA transcription rate. Transcription rates vary from 0 to approximately 3 times the value used in the model producing a total of 10 profiles. The profile curves are produced using Xppaut. We constrained the simulations to a fixed number of 9 steps. Each step corresponds to a specific value Vmax, equally distributed, within the range in which the parameter is allowed to vary. This procedure leads to a total of 10 expression profiles which together with the wild type profile generate the 11 profiles represented in each panel of the figure. The light pink line corresponds to a transcription rate value of 0 followed, in a step wise manner, by darker pink tones, orange, yellow, light and dark green, turquoise, blue and violet as a result of the highest value simulated for the transcription rate. The thick red line shows the expression profile corresponding to the transcription rate used in the wild type (WT) model.