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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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
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dc.title.none.fl_str_mv Epigenomic profiling of primate lymphoblastoid cell lines reveals the evolutionary patterns of epigenetic activities in gene regulatory architectures
title Epigenomic profiling of primate lymphoblastoid cell lines reveals the evolutionary patterns of epigenetic activities in gene regulatory architectures
spellingShingle Epigenomic profiling of primate lymphoblastoid cell lines reveals the evolutionary patterns of epigenetic activities in gene regulatory architectures
García Pérez, Raquel, 1989-
Epigenomics
Molecular evolution
title_short Epigenomic profiling of primate lymphoblastoid cell lines reveals the evolutionary patterns of epigenetic activities in gene regulatory architectures
title_full Epigenomic profiling of primate lymphoblastoid cell lines reveals the evolutionary patterns of epigenetic activities in gene regulatory architectures
title_fullStr Epigenomic profiling of primate lymphoblastoid cell lines reveals the evolutionary patterns of epigenetic activities in gene regulatory architectures
title_full_unstemmed Epigenomic profiling of primate lymphoblastoid cell lines reveals the evolutionary patterns of epigenetic activities in gene regulatory architectures
title_sort Epigenomic profiling of primate lymphoblastoid cell lines reveals the evolutionary patterns of epigenetic activities in gene regulatory architectures
dc.creator.none.fl_str_mv 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-
author García Pérez, Raquel, 1989-
author_facet 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-
author_role author
author2 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-
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Epigenomics
Molecular evolution
topic Epigenomics
Molecular evolution
description 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.
publishDate 2021
dc.date.none.fl_str_mv 2021
2021
2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/48306
http://dx.doi.org/10.1038/s41467-021-23397-1
url http://hdl.handle.net/10230/48306
http://dx.doi.org/10.1038/s41467-021-23397-1
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Nat Commun. 2021;12(1):3116
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info:eu-repo/grantAgreement/ES/1PE/BFU2017-86471-P
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info:eu-repo/grantAgreement/ES/1PE/BFU2016-74961-P
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dc.publisher.none.fl_str_mv Nature Research
publisher.none.fl_str_mv Nature Research
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instname_str Universitat Pompeu Fabra
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spelling Epigenomic profiling of primate lymphoblastoid cell lines reveals the evolutionary patterns of epigenetic activities in gene regulatory architecturesGarcía Pérez, Raquel, 1989-Esteller Cucala, PaulaMas, GlòriaLobon Garcia, IreneDi Carlo, ValerioRiera, MeritxellKuhlwilm, MartinNavarro i Cuartiellas, Arcadi, 1969-Blancher, AntoineDi Croce, LucianoGómez Skarmeta, José LuisJuan, DavidMarquès i Bonet, Tomàs, 1975-EpigenomicsMolecular evolutionChanges 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.R.G.-P. was supported by a fellowship from MICINN (FPU13/01823). P.E.-C. was supported by a Formació de Personal Investigador fellowship from Generalitat de Catalunya (FI_B00122). M.K. was supported by a Deutsche Forschungsgemeinschaft (DFG) fellowship (KU 3467/1-1) and the Postdoctoral Junior Leader Fellowship Program from “la Caixa” Banking Foundation (LCF/BQ/PR19/11700002). D.J. was supported by a Juan de la Cierva fellowship (FJCI2016-29558) from MICINN. T.M-B. is supported by funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement EC-H2020-ERC-CoG-ApeGenomeDiversity-864203), BFU2017-86471-P (AEI/FEDER, UE), “Unidad de Excelencia María de Maeztu”, funded by the AEI (CEX2018-000792-M), Howard Hughes International Early Career, NIH 1R01HG010898-01A1, Obra Social “La Caixa” and Secretaria d’Universitats i Recerca and CERCA Program del Departament d’Economia i Coneixement de la Generalitat de Catalunya (GRC 2017 SGR 880). G.M., V.D.C., and L.D.C. were supported by grants from the Spanish of Economy, Industry, and Competitiveness (MEIC) (BFU2016-75008-P) and G.M. was also supported by the “Convocatoria de Ayudas Fundación BBVA a Investigadores, Innovadores y Creadores Culturales”. J.L.G.-S. was supported by the Spanish government (grants BFU2016-74961-P), an institutional grant Unidad de Excelencia María de Maeztu (MDM-2016-0687) and the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No 740041). A.N. was supported by Fondo Europeo de Desarrollo Regional (FEDER) with project grants BFU2016-77961-P and PGC2018- 101927-B-I00 and by the Spanish National Institute of Bioinformatics (PT17/0009/0020).Nature Research202120212021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/48306http://dx.doi.org/10.1038/s41467-021-23397-1reponame:Repositorio Digital de la UPFinstname:Universitat Pompeu FabraInglésNat Commun. 2021;12(1):3116info:eu-repo/grantAgreement/EC/H2020/864203info:eu-repo/grantAgreement/ES/1PE/BFU2017-86471-Pinfo:eu-repo/grantAgreement/ES/1PE/BFU2016-75008-Pinfo:eu-repo/grantAgreement/ES/1PE/BFU2016-74961-Pinfo:eu-repo/grantAgreement/EC/H2020/740041info:eu-repo/grantAgreement/ES/1PE/BFU2016-77961-Pinfo:eu-repo/grantAgreement/ES/2PE/PGC2018-101927-B-I00© The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repositori.upf.edu:10230/483062026-06-12T07:21:37Z
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