Figure 4. The memory switch model describes the distribution of transcriptional activity.

(A) Promoters can occupy one of four states: Uninduced and Induced (U and I), related to current presence of hormone; and Default and Memory (D and M), associated with prior hormone exposure. The Uninduced state is associated with a basal RNA Pol II rate k_PolB, whereas the Induced state shows two independent RNA Pol II rates k_PolL and k_PolH associated with Default and Memory states, respectively. 20E has two roles: one, to activate transcription by ensuring k_A >> k_-A, as in earlier models; and two, to increase the rate of conversion from Default to Memory by ensuring k_C >> k_-C. The role of Nup98 is to maintain k_C >> k_-C upon withdrawal of 20E. (B–M). Histograms (cyan) show distribution of measured total instantaneous transcriptional activity in normalized units (C.U.), obtained from smFISH of E74 as shown in Figure 1. Lines represent predicted values generated by simulation using best-fitting parameters under the memory switch model.

Figure 4—figure supplement 1. Fitting qPCR data to a four-state model of promoter memory.

(A). Fitting of qPCR data to four-state model under each of four experimental conditions. (B). The rate of recruitment of loci into the active state is similar between all conditions (left). Rapid mRNA accumulation upon second induction in control cells results from the rapid increase in average mRNA production rates. (C). Best fit parameters with 95% confidence intervals. (D). Goodness-of-fit values for Models 1, 2 and the memory switch model. Goodness-of-fit is significantly improved for the memory model compared to either alternate model. (E). Memory model of E74 expression. Fraction of loci in either the default state (dashed lines) or memory state (solid lines) as a function of time. In the presence of Nup98, loci continuously transition into the memory state starting immediately upon 20E exposure.