Insight into genetic predisposition to chronic lymphocytic leukemia from integrative epigenomics.

Genome-wide association studies have provided evidence for inherited genetic predisposition to chronic lymphocytic leukemia (CLL). To gain insight into the mechanisms underlying CLL risk we analyze chromatin accessibility, active regulatory elements marked by H3K27ac, and DNA methylation at 42 risk...

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Autores: Speedy, Helen E., Beekman, Renée, Chapaprieta, Vicente, Orlando, Giulia, Law, Philip J., Martín García, David, Gutiérrez-Abril, Jesús, Catovsky, Daniel, Beà Bobet, Sílvia M., Clot Razquin, Guillem, Puiggròs, Montserrat, Torrents Arenales, David, Puente, Xose S., Allan, James M., López-Otin, Carlos, Campo Güerri, Elias, Houlston, Richard S., Martín-Subero, José Ignacio
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/148038
Acceso en línea:https://hdl.handle.net/2445/148038
Access Level:acceso abierto
Palabra clave:Epigènesi
Leucèmia limfocítica crònica
Cèl·lules B
Epigenesis
Chronic lymphocytic leukemia
B cells
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spelling Insight into genetic predisposition to chronic lymphocytic leukemia from integrative epigenomics.Speedy, Helen E.Beekman, RenéeChapaprieta, VicenteOrlando, GiuliaLaw, Philip J.Martín García, DavidGutiérrez-Abril, JesúsCatovsky, DanielBeà Bobet, Sílvia M.Clot Razquin, GuillemPuiggròs, MontserratTorrents Arenales, DavidPuente, Xose S.Allan, James M.López-Otin, CarlosCampo Güerri, EliasHoulston, Richard S.Martín-Subero, José IgnacioEpigènesiLeucèmia limfocítica crònicaCèl·lules BEpigenesisChronic lymphocytic leukemiaB cellsGenome-wide association studies have provided evidence for inherited genetic predisposition to chronic lymphocytic leukemia (CLL). To gain insight into the mechanisms underlying CLL risk we analyze chromatin accessibility, active regulatory elements marked by H3K27ac, and DNA methylation at 42 risk loci in up to 486 primary CLLs. We identify that risk loci are significantly enriched for active chromatin in CLL with evidence of being CLL-specific or differentially regulated in normal B-cell development. We then use in situ promoter capture Hi-C, in conjunction with gene expression data to reveal likely target genes of the risk loci. Candidate target genes are enriched for pathways related to B-cell development such as MYC and BCL2 signalling. At 14 loci the analysis highlights 63 variants as the probable functional basis of CLL risk. By integrating genetic and epigenetic information our analysis reveals novel insights into the relationship between inherited predisposition and the regulatory chromatin landscape of CLL.Nature Publishing Group2020202020192020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion9 p.application/pdfhttps://hdl.handle.net/2445/148038Articles publicats en revistes (Fonaments Clínics)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1038/s41467-019-11582-2Nature Communications, 2019, vol. 10, num. 1, p. 3615https://doi.org/10.1038/s41467-019-11582-2info:eu-repo/grantAgreement/EC/FP7/282510cc-by (c) Speedy, Helen E. et al., 2019http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:recercat.cat:2445/1480382026-05-29T05:05:01Z
dc.title.none.fl_str_mv Insight into genetic predisposition to chronic lymphocytic leukemia from integrative epigenomics.
title Insight into genetic predisposition to chronic lymphocytic leukemia from integrative epigenomics.
spellingShingle Insight into genetic predisposition to chronic lymphocytic leukemia from integrative epigenomics.
Speedy, Helen E.
Epigènesi
Leucèmia limfocítica crònica
Cèl·lules B
Epigenesis
Chronic lymphocytic leukemia
B cells
title_short Insight into genetic predisposition to chronic lymphocytic leukemia from integrative epigenomics.
title_full Insight into genetic predisposition to chronic lymphocytic leukemia from integrative epigenomics.
title_fullStr Insight into genetic predisposition to chronic lymphocytic leukemia from integrative epigenomics.
title_full_unstemmed Insight into genetic predisposition to chronic lymphocytic leukemia from integrative epigenomics.
title_sort Insight into genetic predisposition to chronic lymphocytic leukemia from integrative epigenomics.
dc.creator.none.fl_str_mv Speedy, Helen E.
Beekman, Renée
Chapaprieta, Vicente
Orlando, Giulia
Law, Philip J.
Martín García, David
Gutiérrez-Abril, Jesús
Catovsky, Daniel
Beà Bobet, Sílvia M.
Clot Razquin, Guillem
Puiggròs, Montserrat
Torrents Arenales, David
Puente, Xose S.
Allan, James M.
López-Otin, Carlos
Campo Güerri, Elias
Houlston, Richard S.
Martín-Subero, José Ignacio
author Speedy, Helen E.
author_facet Speedy, Helen E.
Beekman, Renée
Chapaprieta, Vicente
Orlando, Giulia
Law, Philip J.
Martín García, David
Gutiérrez-Abril, Jesús
Catovsky, Daniel
Beà Bobet, Sílvia M.
Clot Razquin, Guillem
Puiggròs, Montserrat
Torrents Arenales, David
Puente, Xose S.
Allan, James M.
López-Otin, Carlos
Campo Güerri, Elias
Houlston, Richard S.
Martín-Subero, José Ignacio
author_role author
author2 Beekman, Renée
Chapaprieta, Vicente
Orlando, Giulia
Law, Philip J.
Martín García, David
Gutiérrez-Abril, Jesús
Catovsky, Daniel
Beà Bobet, Sílvia M.
Clot Razquin, Guillem
Puiggròs, Montserrat
Torrents Arenales, David
Puente, Xose S.
Allan, James M.
López-Otin, Carlos
Campo Güerri, Elias
Houlston, Richard S.
Martín-Subero, José Ignacio
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Epigènesi
Leucèmia limfocítica crònica
Cèl·lules B
Epigenesis
Chronic lymphocytic leukemia
B cells
topic Epigènesi
Leucèmia limfocítica crònica
Cèl·lules B
Epigenesis
Chronic lymphocytic leukemia
B cells
description Genome-wide association studies have provided evidence for inherited genetic predisposition to chronic lymphocytic leukemia (CLL). To gain insight into the mechanisms underlying CLL risk we analyze chromatin accessibility, active regulatory elements marked by H3K27ac, and DNA methylation at 42 risk loci in up to 486 primary CLLs. We identify that risk loci are significantly enriched for active chromatin in CLL with evidence of being CLL-specific or differentially regulated in normal B-cell development. We then use in situ promoter capture Hi-C, in conjunction with gene expression data to reveal likely target genes of the risk loci. Candidate target genes are enriched for pathways related to B-cell development such as MYC and BCL2 signalling. At 14 loci the analysis highlights 63 variants as the probable functional basis of CLL risk. By integrating genetic and epigenetic information our analysis reveals novel insights into the relationship between inherited predisposition and the regulatory chromatin landscape of CLL.
publishDate 2019
dc.date.none.fl_str_mv 2019
2020
2020
2020
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 https://hdl.handle.net/2445/148038
url https://hdl.handle.net/2445/148038
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1038/s41467-019-11582-2
Nature Communications, 2019, vol. 10, num. 1, p. 3615
https://doi.org/10.1038/s41467-019-11582-2
info:eu-repo/grantAgreement/EC/FP7/282510
dc.rights.none.fl_str_mv cc-by (c) Speedy, Helen E. et al., 2019
http://creativecommons.org/licenses/by/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Speedy, Helen E. et al., 2019
http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 9 p.
application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv Articles publicats en revistes (Fonaments Clínics)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869416433420599296
score 15,811543

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