a, Barplot showing the percentage of human cCREs in the ENCODE4 Registry that were: previously in the ENCODE3 registry (blue), initially called in ENCODE3 but filtered out (orange), new to ENCODE4 (yellow). b, Barplots showing the percentage of cCREs (as defined in a) and size-matched non-cCRE regions (gray) that overlap K562 STARR-seq peaks. c, Line plots depicting average phyloP conservation scores calculated from 240-way Mammalian alignment for +/- 500 bp around each cCRE center stratifying by cCRE group as defined in a. d, Heatscatter plot showing the distribution of ENCODE4 cCREs replicated from ENCODE3 based on their alignment across Zoonomia mammalian genomes. N1 denotes the number of species in which ≥90% of a cCRE aligns; N2 denotes the number of species in which ≤10% of a cCRE aligns. Rectangles indicate predefined groups: Group 1 (G1), highly conserved (N1 ≥ 120, N2 ≤ 25); Group 2 (G2), actively evolving (20 ≤ N1 ≤ 50, N2 ≤ 120); and Group 3 (G3), primate-specific (N1 ≤ 50, N2 ≥ 180). e, Heatscatter plot as in d, but for ENCODE4 cCREs that were filtered out in ENCODE3. f, Heatscatter plot as in d, but for cCREs new in ENCODE4.