A chromatin code for alternative splicing involving a putative association between CTCF and HP1alpha proteins

BACKGROUND: Alternative splicing is primarily controlled by the activity of splicing factors and by the elongation of the RNA polymerase II (RNAPII). Recent experiments have suggested a new complex network of splicing regulation involving chromatin, transcription and multiple protein factors. In par...

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Autores: Agirre Ortiz de Guzmán, Eneritz, 1983-, Bellora Pereyra, Nicolás, Alló, Mariano, Pagès Pinós, Amadís, Bertucci, Paola, Kornblihtt, Alberto R., Eyras Jiménez, Eduardo
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2015
País:España
Recursos:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositório:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/25064
Acesso em linha:http://hdl.handle.net/10230/25064
http://dx.doi.org/10.1186/s12915-015-0141-5
Access Level:Acceso aberto
Palavra-chave:Cromatina
Histones
Regulació genètica
Chromatin
Splicing
Splicing code
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spelling A chromatin code for alternative splicing involving a putative association between CTCF and HP1alpha proteinsAgirre Ortiz de Guzmán, Eneritz, 1983-Bellora Pereyra, NicolásAlló, MarianoPagès Pinós, AmadísBertucci, PaolaKornblihtt, Alberto R.Eyras Jiménez, EduardoCromatinaHistonesRegulació genèticaChromatinSplicingHistonesSplicing codeBACKGROUND: Alternative splicing is primarily controlled by the activity of splicing factors and by the elongation of the RNA polymerase II (RNAPII). Recent experiments have suggested a new complex network of splicing regulation involving chromatin, transcription and multiple protein factors. In particular, the CCCTC-binding factor (CTCF), the Argonaute protein AGO1, and members of the heterochromatin protein 1 (HP1) family have been implicated in the regulation of splicing associated with chromatin and the elongation of RNAPII. These results raise the question of whether these proteins may associate at the chromatin level to modulate alternative splicing. RESULTS:Using chromatin immunoprecipitation sequencing (ChIP-Seq) data for CTCF, AGO1, HP1a, H3K27me3, H3K9me2, H3K36me3, RNAPII, total H3 and 5metC and alternative splicing arrays from two cell lines, we have analyzed the combinatorial code of their binding to chromatin in relation to the alternative splicing patterns between two cell lines, MCF7 and MCF10. Using Machine Learning techniques, we identified the changes in chromatin signals that are most significantly associated with splicing regulation between these two cell lines. Moreover, we have built a map of the chromatin signals on the pre-mRNA, that is, a chromatin-based RNA-map, which can explain 606 (68.55%) of the regulated events between MCF7 and MCF10. This chromatin code involves the presence of HP1a, CTCF, AGO1, RNAPII and histone marks around regulated exons and can differentiate patterns of skipping and inclusion. Additionally, we found a significant association of HP1a and CTCF activities around the regulated exons and a putative DNA binding site for HP1alpha. CONCLUSIONS:Our results show that a considerable number of alternative splicing events could have a chromatin-dependent regulation involving the association of HP1a and CTCF near regulated exons. Additionally, we find further evidence for the involvement of HP1a and AGO1 in chromatin-related splicing regulation.This work was partly supported by the European Alternative Splicing Network (EURASNET). Additionally, E.A, N.B, A.P. and E.E were supported by grants BIO2011-23920 and CSD2009-00080 from MINECO (Spanish Government) and by a grant from the Sandra Ibarra Foundation for Cancer; A.R.K. was supported by grants from the Agencia Nacional de Promoción de Ciencia y Tecnología of Argentina, the University of Buenos Aires, the Howard Hughes Medical Institute; and M.A. by a short term fellowships from EMBO, the Journal of Cell Science and UICC.BioMed Central201520152015info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/25064http://dx.doi.org/10.1186/s12915-015-0141-5reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésBMC biology. 2015;13:31info:eu-repo/grantAgreement/ES/3PN/BIO2011-23920info:eu-repo/grantAgreement/ES/3PN/CSD2009-00080© 2015 Agirre et al.; licensee BioMed Central. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.http://creativecommons.org/licenses/by/4.0info:eu-repo/semantics/openAccessoai:recercat.cat:10230/250642026-05-29T05:05:01Z
dc.title.none.fl_str_mv A chromatin code for alternative splicing involving a putative association between CTCF and HP1alpha proteins
title A chromatin code for alternative splicing involving a putative association between CTCF and HP1alpha proteins
spellingShingle A chromatin code for alternative splicing involving a putative association between CTCF and HP1alpha proteins
Agirre Ortiz de Guzmán, Eneritz, 1983-
Cromatina
Histones
Regulació genètica
Chromatin
Splicing
Histones
Splicing code
title_short A chromatin code for alternative splicing involving a putative association between CTCF and HP1alpha proteins
title_full A chromatin code for alternative splicing involving a putative association between CTCF and HP1alpha proteins
title_fullStr A chromatin code for alternative splicing involving a putative association between CTCF and HP1alpha proteins
title_full_unstemmed A chromatin code for alternative splicing involving a putative association between CTCF and HP1alpha proteins
title_sort A chromatin code for alternative splicing involving a putative association between CTCF and HP1alpha proteins
dc.creator.none.fl_str_mv Agirre Ortiz de Guzmán, Eneritz, 1983-
Bellora Pereyra, Nicolás
Alló, Mariano
Pagès Pinós, Amadís
Bertucci, Paola
Kornblihtt, Alberto R.
Eyras Jiménez, Eduardo
author Agirre Ortiz de Guzmán, Eneritz, 1983-
author_facet Agirre Ortiz de Guzmán, Eneritz, 1983-
Bellora Pereyra, Nicolás
Alló, Mariano
Pagès Pinós, Amadís
Bertucci, Paola
Kornblihtt, Alberto R.
Eyras Jiménez, Eduardo
author_role author
author2 Bellora Pereyra, Nicolás
Alló, Mariano
Pagès Pinós, Amadís
Bertucci, Paola
Kornblihtt, Alberto R.
Eyras Jiménez, Eduardo
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Cromatina
Histones
Regulació genètica
Chromatin
Splicing
Histones
Splicing code
topic Cromatina
Histones
Regulació genètica
Chromatin
Splicing
Histones
Splicing code
description BACKGROUND: Alternative splicing is primarily controlled by the activity of splicing factors and by the elongation of the RNA polymerase II (RNAPII). Recent experiments have suggested a new complex network of splicing regulation involving chromatin, transcription and multiple protein factors. In particular, the CCCTC-binding factor (CTCF), the Argonaute protein AGO1, and members of the heterochromatin protein 1 (HP1) family have been implicated in the regulation of splicing associated with chromatin and the elongation of RNAPII. These results raise the question of whether these proteins may associate at the chromatin level to modulate alternative splicing. RESULTS:Using chromatin immunoprecipitation sequencing (ChIP-Seq) data for CTCF, AGO1, HP1a, H3K27me3, H3K9me2, H3K36me3, RNAPII, total H3 and 5metC and alternative splicing arrays from two cell lines, we have analyzed the combinatorial code of their binding to chromatin in relation to the alternative splicing patterns between two cell lines, MCF7 and MCF10. Using Machine Learning techniques, we identified the changes in chromatin signals that are most significantly associated with splicing regulation between these two cell lines. Moreover, we have built a map of the chromatin signals on the pre-mRNA, that is, a chromatin-based RNA-map, which can explain 606 (68.55%) of the regulated events between MCF7 and MCF10. This chromatin code involves the presence of HP1a, CTCF, AGO1, RNAPII and histone marks around regulated exons and can differentiate patterns of skipping and inclusion. Additionally, we found a significant association of HP1a and CTCF activities around the regulated exons and a putative DNA binding site for HP1alpha. CONCLUSIONS:Our results show that a considerable number of alternative splicing events could have a chromatin-dependent regulation involving the association of HP1a and CTCF near regulated exons. Additionally, we find further evidence for the involvement of HP1a and AGO1 in chromatin-related splicing regulation.
publishDate 2015
dc.date.none.fl_str_mv 2015
2015
2015
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/10230/25064
http://dx.doi.org/10.1186/s12915-015-0141-5
url http://hdl.handle.net/10230/25064
http://dx.doi.org/10.1186/s12915-015-0141-5
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv BMC biology. 2015;13:31
info:eu-repo/grantAgreement/ES/3PN/BIO2011-23920
info:eu-repo/grantAgreement/ES/3PN/CSD2009-00080
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by/4.0
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv BioMed Central
publisher.none.fl_str_mv BioMed Central
dc.source.none.fl_str_mv 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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