Fig. 2: The promoter on rate is a sigmoidal function of enhancer–promoter contact probabilities.
From: Nonlinear control of transcription through enhancer–promoter interactions
a, Capture-C (6.4 kb resolution) analysis of the founder cell line used for the experiments in Fig. 1 after converting read counts into contact probabilities (top) (Methods). Bottom, cross-section showing contact probabilities from the ectopic Sox2 transgene. Insets: magnification of contact probability across the TAD boundaries. b, Mean eGFP mRNA numbers per cell plotted against contact probabilities between the ectopic Sox2 promoter and SCR insertions. The red dots show individual cell lines. The black dots show the average values within equally spaced 20 kb bins ± s.d. The number of cell lines per bin varies from 1 to 28. c, Representative smRNA-FISH images from cell lines in which eGFP transcription is driven by the Sox2 promoter alone (left) or by the SCR located at different distances and contact probabilities (right). Scale bar, 10 µm. d, Distributions of mRNA numbers per cell measured in the cell lines shown in c. The error bars show the minimum and maximum frequency. n = 3 technical replicates. The line shows the best fit of the phenomenological two-state model to the experimental data shown in b and d. e, Best fit to experimental data of b and d. Best-fit parameters are shown in Extended Data Fig. 3b. f, Description of the phenomenological two-state model with a variable on rate. The Hill function describes the dependency of kon on contact probability (pc). \({k}_{{\rm{on}}}^{0}\) and \({k}_{{\rm{on}}}^{1}\) are the minimum and maximum on rates, respectively; c and h are the Hill function critical threshold and the sensitivity parameter, respectively. ∅ symbolizes degraded RNA. g, The best-fitting Hill function for kon (in units of mRNA lifetime δ), corresponding to a sigmoidal curve. h, Close-up of e, highlighting the predicted insulation outside the TAD boundaries (red and green shaded areas). Data are presented as in b.
