Figure 5. Compensation in Nonparalogous Genes May Contribute to Oscillator Robustness.
(A) U-2 OS cells transfected with siRNAs targeting Bmal1 or Cry1, individually or in combination as indicated, were synchronized, and luminescence levels were measured over 5 d. Data are representative of three independent biological replicates. Note that two examples are shown for the siCry1/siBmal1 combination knockdown.
(B) Median and ranges of amplitude following single or combinatoric perturbation. The amplitude of the circadian signal was estimated using continuous wavelet decomposition and averaged across three replicates in three independent experiments. The median and range of the fold changes relative to the negative siRNA control are plotted. Both individual siRNA treatments are significantly down-regulated relative to the negative siRNA controls (p < 0.05, Mann-Whitney test), and the siCry1/siBmal1 double knockdown is also significantly down-regulated relative to siCry1 (p < 0.05, Mann-Whitney test).
