a, Density plots depicting STARR scores for silencer cCREs in six STARR-seq libraries stratified by category: REST+ enhancer/silencer (yellow) REST+ silencer (purple), stringent STARR silencer (dark blue), robust STARR silencer (light blue). All silencer distributions are significantly shifted compared to the background of all cCREs (gray). P-values, all < 2.2 × 10−16 , are calculated from a pairwise, two-sided Wilcoxon rank sum test with FDR correction. b, Barplots depicting the number of robust STARR silencer cCREs stratified by cCREs class. c, Barplots depicting the enrichment for cCRE classes of robust STARR silencer cCRE compared to the entire Registry. d, Heatmap depicting the overlap of STARR silencer cCREs with binding sites for TRIM28, ZNF280A, SETDB1, REST, MIER1 and ZNF146 (DNA binding proteins enriched in STARR silencers, Supplementary Table 11d). Hierarchical clustering reveals two distinct clusters of STARR silencer cCREs based on ChIP-seq peak overlap. e, Nested violin-boxplots showing gene expression in K562 cells for the nearest gene of different classes and categories of cCREs. On the left are cCREs annotated in K562 based on K562-specific chromatin signatures including promoter, proximal enhancer, distal enhancer and low chromatin accessibility (CA) cCREs. On the right are STARR silencer cCREs stratified by threshold categories. Medians are shown above each distribution. P-values are calculated from a pairwise, two-sided Wilcoxon rank sum test with FDR correction.