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 35 extensively profiled a new panel of human, chimpanzee, gorilla, orangutan and macaque 36 lymphoblastoid cell lines, using ChIP-seq for five histone marks, ATAC-seq and RNA-seq, further 37 complemented with WGS and WGBS. We annotated regulatory elements and integrated chromatin 38 contact maps to define gene regulatory architectures, creating the largest catalog of regulatory 39 elements in primates to date. We highlight the role of promoters and intragenic enhancers in 40 epigenetically coordinated gene regulatory architectures. We also observe that epigenetic 41 conservation and its correlation with sequence conservation depends on the activity state of the 42 regulatory element. Remarkably, we find that novel human-specific intragenic enhancers with weak 43 activities are enriched in human-specific mutations and appear in genes with signals of positive 44 selection, tissue-specific expression and specific functional enrichments, suggesting that these genes 45 may have contributed to important human adaptations. 46 47 we the study regulatory evolution in the human lineage. Further will be needed to clarify the specific role of these elements in different tissues and cell types.