Figure 1. A transcriptional bursting model is able to mimic the rare coordinated high states observed in drug naive melanoma.

(A) Drug naive melanoma cells exist in low (white cells) as well as rare coordinated high (blue cells) states. Cells in the rare coordinated high state characterize the pre-resistant state observed in drug naive melanoma. A schematic of the corresponding expression pattern is shown in the panel below. The cells in a high expression state are more likely to survive and acquire resistance upon drug administration.

(B) Schematic of the constitutive model for two nodes. Gene product is either produced at rate r_prod or degraded with rate r_deg. Gene regulation is modeled by a Hill function, where the gene product count of the regulating gene A increases the production rate of the gene product of the regulated gene B.

(C) Schematic of the transcriptional bursting model for two nodes. DNA is either in an inactive (off) or active (on) state. Transitions take place with rates r_on and r_off, where gene product is synthesized with rates r_pod and d*r_prod, respectively, d>1. Gene product degrades with rate r_deg. Gene regulation is modeled by a Hill function, where the gene expression of the regulating gene A increases the activation of the DNA of the regulated gene B.

(D-G) Depending on the network and the parameters of the transcriptional bursting model, we observe stably low expression (D), stably high expression (E), uncoordinated transient high expression (F) and rare transient coordinated high expression (G).

See also Figure S1.