The epigenetic landscape of Alu repeats delineates the structural and functional genomic architecture of colon cancer cells

Cancer cells exhibit multiple epigenetic changes with prominent local DNA hypermethylation and widespread hypomethylation affecting large chromosomal domains. Epigenome studies often disregard the study of repeat elements owing to technical complexity and their undefined role in genome regulation. W...

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Autores: Jordà Ramos, Mireia, Díez Villanueva, Anna, Mallona, Izaskun, Martín, Berta, Lois Olmo, Sergio, Barrera, Víctor, Esteller, Manel, Vavouri, Tanya, Peinado Morales, Miguel Á. (Miguel Ángel)
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2017
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:2445/120046
Acceso en línea:https://hdl.handle.net/2445/120046
Access Level:acceso abierto
Palabra clave:Cèl·lules canceroses
Epigenètica
Càncer colorectal
Cancer cells
Epigenetics
Colorectal cancer
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spelling The epigenetic landscape of Alu repeats delineates the structural and functional genomic architecture of colon cancer cellsJordà Ramos, MireiaDíez Villanueva, AnnaMallona, IzaskunMartín, BertaLois Olmo, SergioBarrera, VíctorEsteller, ManelVavouri, TanyaPeinado Morales, Miguel Á. (Miguel Ángel)Cèl·lules cancerosesEpigenèticaCàncer colorectalCancer cellsEpigeneticsColorectal cancerCancer cells exhibit multiple epigenetic changes with prominent local DNA hypermethylation and widespread hypomethylation affecting large chromosomal domains. Epigenome studies often disregard the study of repeat elements owing to technical complexity and their undefined role in genome regulation. We have developed NSUMA (Next-generation Sequencing of UnMethylated Alu), a cost-effective approach allowing the unambiguous interrogation of DNA methylation in more than 130,000 individual Alu elements, the most abundant retrotransposon in the human genome. DNA methylation profiles of Alu repeats have been analyzed in colon cancers and normal tissues using NSUMA and whole-genome bisulfite sequencing. Normal cells show a low proportion of unmethylated Alu (1%-4%) that may increase up to 10-fold in cancer cells. In normal cells, unmethylated Alu elements tend to locate in the vicinity of functionally rich regions and display epigenetic features consistent with a direct impact on genome regulation. In cancer cells, Alu repeats are more resistant to hypomethylation than other retroelements. Genome segmentation based on high/low rates of Alu hypomethylation allows the identification of genomic compartments with differential genetic, epigenetic, and transcriptomic features. Alu hypomethylated regions show low transcriptional activity, late DNA replication, and its extent is associated with higher chromosomal instability. Our analysis demonstrates that Alu retroelements contribute to define the epigenetic landscape of normal and cancer cells and provides a unique resource on the epigenetic dynamics of a principal, but largely unexplored, component of the primate genome.Cold Spring Harbor Laboratory Press2018201820172018info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion15 p.application/pdfhttps://hdl.handle.net/2445/120046Articles publicats en revistes (Ciències Fisiològiques)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/10.1101/gr.207522.116Genome Research, 2017, vol. 27, p. 118-132https://doi.org/10.1101/gr.207522.116(c) Jordà, Mireia et al., 2017info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1200462026-05-29T05:05:01Z
dc.title.none.fl_str_mv The epigenetic landscape of Alu repeats delineates the structural and functional genomic architecture of colon cancer cells
title The epigenetic landscape of Alu repeats delineates the structural and functional genomic architecture of colon cancer cells
spellingShingle The epigenetic landscape of Alu repeats delineates the structural and functional genomic architecture of colon cancer cells
Jordà Ramos, Mireia
Cèl·lules canceroses
Epigenètica
Càncer colorectal
Cancer cells
Epigenetics
Colorectal cancer
title_short The epigenetic landscape of Alu repeats delineates the structural and functional genomic architecture of colon cancer cells
title_full The epigenetic landscape of Alu repeats delineates the structural and functional genomic architecture of colon cancer cells
title_fullStr The epigenetic landscape of Alu repeats delineates the structural and functional genomic architecture of colon cancer cells
title_full_unstemmed The epigenetic landscape of Alu repeats delineates the structural and functional genomic architecture of colon cancer cells
title_sort The epigenetic landscape of Alu repeats delineates the structural and functional genomic architecture of colon cancer cells
dc.creator.none.fl_str_mv Jordà Ramos, Mireia
Díez Villanueva, Anna
Mallona, Izaskun
Martín, Berta
Lois Olmo, Sergio
Barrera, Víctor
Esteller, Manel
Vavouri, Tanya
Peinado Morales, Miguel Á. (Miguel Ángel)
author Jordà Ramos, Mireia
author_facet Jordà Ramos, Mireia
Díez Villanueva, Anna
Mallona, Izaskun
Martín, Berta
Lois Olmo, Sergio
Barrera, Víctor
Esteller, Manel
Vavouri, Tanya
Peinado Morales, Miguel Á. (Miguel Ángel)
author_role author
author2 Díez Villanueva, Anna
Mallona, Izaskun
Martín, Berta
Lois Olmo, Sergio
Barrera, Víctor
Esteller, Manel
Vavouri, Tanya
Peinado Morales, Miguel Á. (Miguel Ángel)
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Cèl·lules canceroses
Epigenètica
Càncer colorectal
Cancer cells
Epigenetics
Colorectal cancer
topic Cèl·lules canceroses
Epigenètica
Càncer colorectal
Cancer cells
Epigenetics
Colorectal cancer
description Cancer cells exhibit multiple epigenetic changes with prominent local DNA hypermethylation and widespread hypomethylation affecting large chromosomal domains. Epigenome studies often disregard the study of repeat elements owing to technical complexity and their undefined role in genome regulation. We have developed NSUMA (Next-generation Sequencing of UnMethylated Alu), a cost-effective approach allowing the unambiguous interrogation of DNA methylation in more than 130,000 individual Alu elements, the most abundant retrotransposon in the human genome. DNA methylation profiles of Alu repeats have been analyzed in colon cancers and normal tissues using NSUMA and whole-genome bisulfite sequencing. Normal cells show a low proportion of unmethylated Alu (1%-4%) that may increase up to 10-fold in cancer cells. In normal cells, unmethylated Alu elements tend to locate in the vicinity of functionally rich regions and display epigenetic features consistent with a direct impact on genome regulation. In cancer cells, Alu repeats are more resistant to hypomethylation than other retroelements. Genome segmentation based on high/low rates of Alu hypomethylation allows the identification of genomic compartments with differential genetic, epigenetic, and transcriptomic features. Alu hypomethylated regions show low transcriptional activity, late DNA replication, and its extent is associated with higher chromosomal instability. Our analysis demonstrates that Alu retroelements contribute to define the epigenetic landscape of normal and cancer cells and provides a unique resource on the epigenetic dynamics of a principal, but largely unexplored, component of the primate genome.
publishDate 2017
dc.date.none.fl_str_mv 2017
2018
2018
2018
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/2445/120046
url https://hdl.handle.net/2445/120046
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/10.1101/gr.207522.116
Genome Research, 2017, vol. 27, p. 118-132
https://doi.org/10.1101/gr.207522.116
dc.rights.none.fl_str_mv (c) Jordà, Mireia et al., 2017
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) Jordà, Mireia et al., 2017
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 15 p.
application/pdf
dc.publisher.none.fl_str_mv Cold Spring Harbor Laboratory Press
publisher.none.fl_str_mv Cold Spring Harbor Laboratory Press
dc.source.none.fl_str_mv Articles publicats en revistes (Ciències Fisiològiques)
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
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score 15,812429

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