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...

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Detalles Bibliográficos
Autores: García Perez, Raquel|||0000-0002-2573-6984, Esteller-Cucala, Paula|||0000-0003-3048-4280, Mas, Glòria, Lobón, Irene|||0000-0003-1170-9915, Di Carlo, Valerio|||0000-0002-5099-0685, Riera, Meritxell, Kuhlwilm, Martin|||0000-0002-0115-1797, Navarro, Arcadi|||0000-0003-2162-8246, Blancher, Antoine|||0000-0002-6763-0539, Di Croce, Luciano|||0000-0003-3488-6228, Gomez-Skarmeta, José Luis, Juan, David|||0000-0003-1912-9667, Marquès i Bonet, Tomàs|||0000-0002-5597-3075
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:242993
Acceso en línea:https://ddd.uab.cat/record/242993
https://dx.doi.org/urn:doi:10.1038/s41467-021-23397-1
Access Level:acceso abierto
Descripción
Sumario: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.