Fig. 2. Most SOX9-dependent REs are buffered in their response to SOX9 dosage changes, with a sensitive subset.

a, Loadings from PC analysis of ATAC-seq CPM of all 151,457 REs across all CNCC samples (see Extended Data Fig. 2a), corrected for differentiation batch and plotted as a function of estimated relative SOX9 dosage (shown as percentage relative to no dTAG^V-1). Black line represents Hill equation fit. Points are biological (differentiation or clone) replicates. b, Example ATAC-seq browser tracks of individual RE accessibility at different SOX9 dosages (y axis, normalized coverage in 10-bp bins, identical range in all browser tracks), averaged across all replicates at each dosage. c, Schematic of approach to model nonlinearity of SOX9-dependent REs. a and b in linear model refer to slope and intercept, respectively. a and b in Hill equation refer to ED₅₀ and Hill exponent, respectively. d, Illustration of different ED₅₀ and Hill exponent values on theoretical Hill equation curves. e, Individual REs from b with replicates, fitted by Hill equation (black line). f, Histogram of ΔAIC of all 35,713 SOX9-dependent REs. Red line indicates ΔAIC = 2. g, Scatterplot of ED₅₀ and Hill exponent of 23,414 SOX9-dependent REs with good fit (P < 0.05 for both parameters).