Fig. 2.

Transcriptional bursting yields intrinsic variation for each gene across cells at steady state. (A) Two-state model of transcriptional bursting and regulation for one Regulator–Target pair. Variables: k_ON (burst frequency), k_OFF (1/burst duration), s_RNA (transcription = burst size*k_OFF), s_protein (translation), δ (decay), Ø (no molecules left). Blue: TF, red: Target. (B) Simulation of TF^(RNA), TF^(P), and Target^(RNA) bursting events and abundance for one cell in the presence of direct regulation between a pair of genes. (C) Abundance distributions of TF^(RNA) (μ: 29, CV: 0.84), TF^(P) in thousands (μ: 61, CV: 0.31), and Target^(RNA) (μ: 50, CV: 0.93), for median values of burst parameters, across 20,000 simulated cells. (D) Overdispersion structure (variance/mean) of total mRNA for TF and Target for different burst sizes (large TF: 32 transcripts/burst, large Target: 40 transcripts/burst; small TF: 3, small Target: 4). (E) Mean TF^(RNA) (Top), TF^(P) (Middle), and Target^(RNA) (Bottom) abundance over time, across cells that did have a burst of the TF gene (colored, n = 715) versus those that did not have a burst (gray, n = 715 randomly subsampled cells with no burst) at t = 0 (20,000 total cells). Solid red line indicates TF^(RNA) and dashed red line indicates TF^(ΔRNA). Curves are based on data points at 30 min intervals. (TF mRNA at 30 min shows a sharp peak due to discrete sampling; the actual peak is smooth.)