TF occupancy at synergy and buffer gene sets, showing proportion of genes with one or more RE bound by GATA1 or SPI1 including promoter (within 1 kb) or any ABC model 45 predicted enhancer (left) and log 2 FC of promoter or average log 2 FC within enhancers (right). Includes all annotated genes with non-zero ChIP-seq reads. Each dot is the average signal across all bound REs for one gene. Additive set: subset of 50 genes with most additive phenotype. Gene set sizes from left to right: n =300, 50, 53 and 55. n = 141900 (two biological replicates, one additional technical replicate). dg, ik, Significance cutoffs for DE genes are abs(log 2 FC) > 0.5, P adj < 0.05; DE gene testing for each gRNA group is against NTC. All gRNA groups have n > 34 (b, c) and n > 59 (dk) cells. Logistic regression was used for DE gene testing. e, One-sided Fishers exact test. f, k, Box plot, median and interquartile range (IQR). Box whiskers, 1.5 IQR. Two-sided Wilcoxon test. Significance cutoffs: NS P > 0.05, * P < 0.05, ** P < 0.01, *** P < 0.001, **** P < 0.0001. GS, gene set; norm., normalized; NS, not significant.