Fig. 4. Housekeeping enhancers are additive and developmental enhancers are super-additive independently of the CP type.

a Scatterplots showing predicted activities (x-axis) based on an additive (left) or a multiplicative model (right) versus observed activities (y-axis) using the RpS12 housekeeping CP. Corresponding R-squared (R²) values are shown (top left), and enhancer pairs in which both candidate sequences are active are highlighted using density lines (in orange). Identity lines are shown using dotted lines (x = y). b Fraction of enhancer pairs (in which both candidate sequences are active) for which the additive (in white) or the multiplicative (in blue) predicted values were the most accurate. c Selected housekeeping (left) and developmental (right) enhancer pairs with comparable 5’ and 3’ individual activities, either with a housekeeping (hkCP, in red) or a developmental (dCP, in green) Core Promoter. For each pair, individual and combined measured activities are shown (solid gray bars) and compared to predicted activities (striped bars) using either the additive (Pred. add.) or the fitted multiplicative (Pred. fit. mult.) model. Bar heights correspond to the mean activity values and whiskers to the standard deviations. d Expected additive and observed activities of housekeeping versus developmental enhancer pairs (x-axis) using either a housekeeping (hkCP, in red) or a developmental (dCP, in green) CP. n = 3590, 2392, 3513 and 2328 pairs, respectively. Two-sided Wilcoxon test P-values are shown; box plots show the median (line), upper and lower quartiles (box) ±1.5× interquartile range (whiskers), outliers are not shown.