Figure 2. Perturbation analysis revealed two principles of clock function, proportionality and paralog compensation.

(A) Proportionality. Knockdown of a transcriptional activator, Gene “A”, results in linear and proportional changes in genes “X”, “Y”, and “Z”. While “X” and “Y” go down in response to knock down of gene “A”, consistent with a role of gene “A” as an activator of those genes, gene “Z” goes up, indicating a repressive relationship between gene “A” and gene “Z”. (B) Paralog Compensation. Given a family of paralogous transcriptional repressors, R1, R2, and R3, and a regulatory architecture where R2 harbors the response element bound by this family, the following responses occur following knockdown of R1: R2 goes up, R3 is unchanged.