Figure 7. Feedback-first regulation is conserved in human cells.

(A) Schematic diagram of G1/S regulation in human cells. (B) Cyclin E1 activation is consistent in 4 different cell cycle synchronized microarray experiments from Whitfield et al. (2002). The standard deviation σ and the standard error of the mean (SEM) is calculated for each gene. (C) 7 genes regulated by the E2F family of transcription factors are activated at different times; data shown from a single dataset. The vertical and horizontal bars indicate the mean activation time and the SEM respectively. (D) Gene activation time correlation between 2 datasets (R² = 0.52). (E) Cumulative distribution of mean activation times for cell cycle regulated E2F-targets. Genes responsible for positive feedback at the G1/S transition, including the cyclins E1 and E2 the transcription factor E2F1, and the SCF component Skp2, are transcribed earlier than other E2F-targets (p<0.01) and earlier than the set of E2F targets specifically involved in DNA replication (p=0.03). This demonstrates the conservation of feedback-first regulation in eukaryotes.