Epigenomic profiling of primate LCLs reveals the coordinated evolution of gene expression and epigenetic signals in regulatory architectures

To gain insight into the evolution of the epigenetic regulation of gene expression in primates, we extensively profiled a new panel of human, chimpanzee, gorilla, orangutan and macaque lymphoblastoid cell lines, using ChIP-seq for five histone marks, ATAC-seq and RNA-seq, further complemented with WGS and WGBS. We annotated regulatory elements and integrated chromatin contact maps to define gene regulatory architectures, creating the largest catalog of regulatory elements in primates to date. We highlight the role of promoters and intragenic enhancers in epigenetically coordinated gene regulatory architectures. We also observe that epigenetic conservation and its correlation with sequence conservation depends on the activity state of the regulatory element. Remarkably, we find that novel human-specific intragenic enhancers with weak activities are enriched in human-specific mutations and appear in genes with signals of positive selection, tissue-specific expression and specific functional enrichments, suggesting that these genes may have contributed to important human adaptations.