Epigenomic profiling of primate lymphoblastoid cell lines reveals the evolutionary patterns of epigenetic activities in gene regulatory architectures

Changes in the epigenetic regulation of gene expression have a central role in evolution. Here, we extensively profiled a panel of human, chimpanzee, gorilla, orangutan, and macaque lymphoblastoid cell lines (LCLs), using ChIP-seq for five histone marks, ATAC-seq and RNA-seq, further complemented wi...

ver descrição completa

Detalhes bibliográficos
Autores: García Pérez, Raquel, 1989-, Esteller Cucala, Paula, Mas, Glòria, Lobon Garcia, Irene, Di Carlo, Valerio, Riera, Meritxell, Kuhlwilm, Martin, Navarro i Cuartiellas, Arcadi, 1969-, Blancher, Antoine, Di Croce, Luciano, Gómez Skarmeta, José Luis, Juan, David, Marquès i Bonet, Tomàs, 1975-
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Recursos:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/48306
Acesso em linha:http://hdl.handle.net/10230/48306
http://dx.doi.org/10.1038/s41467-021-23397-1
Access Level:acceso abierto
Palavra-chave:Epigenomics
Molecular evolution
Descrição
Resumo:Changes in the epigenetic regulation of gene expression have a central role in evolution. Here, we extensively profiled a panel of human, chimpanzee, gorilla, orangutan, and macaque lymphoblastoid cell lines (LCLs), using ChIP-seq for five histone marks, ATAC-seq and RNA-seq, further complemented with whole genome sequencing (WGS) and whole genome bisulfite sequencing (WGBS). We annotated regulatory elements (RE) and integrated chromatin contact maps to define gene regulatory architectures, creating the largest catalog of RE in primates to date. We report that epigenetic conservation and its correlation with sequence conservation in primates depends on the activity state of the regulatory element. Our gene regulatory architectures reveal the coordination of different types of components and highlight the role of promoters and intragenic enhancers (gE) in the regulation of gene expression. We observe that most regulatory changes occur in weakly active gE. Remarkably, novel human-specific gE with weak activities are enriched in human-specific nucleotide changes. These elements appear in genes with signals of positive selection and human acceleration, tissue-specific expression, and particular functional enrichments, suggesting that the regulatory evolution of these genes may have contributed to human adaptation.