Fig. 3: Evolution and functionality of the pTE-derived enhancer-associated NF-κB motifs.

a Proportional contribution of sequence types to TFBS in enhancers, with pTE-derived TFBS highlighted in color. Left: TFBS shared with macaque. Right: great-ape-specific TFBS (fully contained within genomic gaps in RheMac10 relative to GRCh38). b Fraction of NF-κB-bound TFBS (fully embedded within ChIP-seq peaks) within each pTE biotype. c Contribution of enhancer sequence categories to NF-κB-bound motifs; pTEs highlighted. d Enrichment/depletion of Alu- or pERV-derived NF-κB motifs embedded within NF-κB ChIP-seq peaks, relative to the same motifs within ETS1 and RUNX1 ChIP-seq peaks assessed using two-sided Fisher’s exact test. e Distribution of NF-κB ChIP-seq signal centered on Alu and pERV-derived motifs. f Left: NF-κB motifs identified in consensus sequences of pTE subfamilies most abundant within NF-κB ChIP-seq peaks (>100 copies). P-values are computed by FIMO (MEME suite) with Benjamini-Hochberg correction; P <  0.0001 is considered a stringent match (black) and P < 0.001 a permissive match (gray). Middle: fraction of enhancer-localized pTEs carrying each distinct NF-κB motif. Right: Fraction of pTEs in enhancers carrying any of the four NF-κB motifs. g Left panels: predicted binding affinity differences (Δ) for shared pTE-derived NF-κB1 motifs (MA00105.4) between human and macaque/chimpanzee genomes (TFBStools). Right panels: Δ for great-ape-specific motifs relative to chimpanzee orthologs and consensus sequences. Inflammation-related motifs are highlighted in red throughout. Primate icons are created in BioRender. Zueva, E. (2025) https://BioRender.com/8d7b1bb. Source data are provided as a Source Data file.