A chromatin code for alternative splicing involving a putative association between CTCF and HP1aα proteins

Autores
Agirre, Eneritz; Bellora, Nicolás; Alló, Mariano; Pagès, Amadís; Bertucci, Paola Yanina; Kornblihtt, Alberto Rodolfo; Eyras, Eduardo
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
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, HP1aα, 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 HP1aα, CTCF, AGO1, RNAPII and histone marks around regulated exons and can differentiate patterns of skipping and inclusion. Additionally, we found a significant association of HP1aα and CTCF activities around the regulated exons and a putative DNA binding site for HP1aα. Conclusions: Our results show that a considerable number of alternative splicing events could have a chromatin-dependent regulation involving the association of HP1aα and CTCF near regulated exons. Additionally, we find further evidence for the involvement of HP1aα and AGO1 in chromatin-related splicing regulation.
Fil: Agirre, Eneritz. Universitat Pompeu Fabra; España. Centre National de la Recherche Scientifique; Francia. Institute of Human Genetics; Francia
Fil: Bellora, Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigaciones en Biodiversidad y Medioambiente. Universidad Nacional del Comahue. Centro Regional Universidad Bariloche. Instituto de Investigaciones en Biodiversidad y Medioambiente; Argentina. Universitat Pompeu Fabra; España
Fil: Alló, Mariano. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina. European Molecular Biology Laboratory; Alemania
Fil: Pagès, Amadís. Universitat Pompeu Fabra; España
Fil: Bertucci, Paola Yanina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina. European Molecular Biology Laboratory; Alemania
Fil: Kornblihtt, Alberto Rodolfo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
Fil: Eyras, Eduardo. Universitat Pompeu Fabra; España. Institució Catalana de Recerca i Estudis Avancats; España
Materia
CHROMATIN
HISTONES
SPLICING
SPLICING CODE
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/85531
Acceder
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repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling A chromatin code for alternative splicing involving a putative association between CTCF and HP1aα proteinsAgirre, EneritzBellora, NicolásAlló, MarianoPagès, AmadísBertucci, Paola YaninaKornblihtt, Alberto RodolfoEyras, EduardoCHROMATINHISTONESSPLICINGSPLICING CODEhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Background: 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, HP1aα, 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 HP1aα, CTCF, AGO1, RNAPII and histone marks around regulated exons and can differentiate patterns of skipping and inclusion. Additionally, we found a significant association of HP1aα and CTCF activities around the regulated exons and a putative DNA binding site for HP1aα. Conclusions: Our results show that a considerable number of alternative splicing events could have a chromatin-dependent regulation involving the association of HP1aα and CTCF near regulated exons. Additionally, we find further evidence for the involvement of HP1aα and AGO1 in chromatin-related splicing regulation.Fil: Agirre, Eneritz. Universitat Pompeu Fabra; España. Centre National de la Recherche Scientifique; Francia. Institute of Human Genetics; FranciaFil: Bellora, Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigaciones en Biodiversidad y Medioambiente. Universidad Nacional del Comahue. Centro Regional Universidad Bariloche. Instituto de Investigaciones en Biodiversidad y Medioambiente; Argentina. Universitat Pompeu Fabra; EspañaFil: Alló, Mariano. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina. European Molecular Biology Laboratory; AlemaniaFil: Pagès, Amadís. Universitat Pompeu Fabra; EspañaFil: Bertucci, Paola Yanina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina. European Molecular Biology Laboratory; AlemaniaFil: Kornblihtt, Alberto Rodolfo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Eyras, Eduardo. Universitat Pompeu Fabra; España. Institució Catalana de Recerca i Estudis Avancats; EspañaBioMed Central2015-12-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/85531Agirre, Eneritz; Bellora, Nicolás; Alló, Mariano; Pagès, Amadís; Bertucci, Paola Yanina; et al.; A chromatin code for alternative splicing involving a putative association between CTCF and HP1aα proteins; BioMed Central; Bmc Biology; 13; 1; 2-12-2015; 1-141741-7007CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1186/s12915-015-0141-5info:eu-repo/semantics/altIdentifier/url/https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-015-0141-5info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:02:05Zoai:ri.conicet.gov.ar:11336/85531instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 10:02:05.251CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv A chromatin code for alternative splicing involving a putative association between CTCF and HP1aα proteins
title A chromatin code for alternative splicing involving a putative association between CTCF and HP1aα proteins
spellingShingle A chromatin code for alternative splicing involving a putative association between CTCF and HP1aα proteins
Agirre, Eneritz
CHROMATIN
HISTONES
SPLICING
SPLICING CODE
title_short A chromatin code for alternative splicing involving a putative association between CTCF and HP1aα proteins
title_full A chromatin code for alternative splicing involving a putative association between CTCF and HP1aα proteins
title_fullStr A chromatin code for alternative splicing involving a putative association between CTCF and HP1aα proteins
title_full_unstemmed A chromatin code for alternative splicing involving a putative association between CTCF and HP1aα proteins
title_sort A chromatin code for alternative splicing involving a putative association between CTCF and HP1aα proteins
dc.creator.none.fl_str_mv Agirre, Eneritz
Bellora, Nicolás
Alló, Mariano
Pagès, Amadís
Bertucci, Paola Yanina
Kornblihtt, Alberto Rodolfo
Eyras, Eduardo
author Agirre, Eneritz
author_facet Agirre, Eneritz
Bellora, Nicolás
Alló, Mariano
Pagès, Amadís
Bertucci, Paola Yanina
Kornblihtt, Alberto Rodolfo
Eyras, Eduardo
author_role author
author2 Bellora, Nicolás
Alló, Mariano
Pagès, Amadís
Bertucci, Paola Yanina
Kornblihtt, Alberto Rodolfo
Eyras, Eduardo
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv CHROMATIN
HISTONES
SPLICING
SPLICING CODE
topic CHROMATIN
HISTONES
SPLICING
SPLICING CODE
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv 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, HP1aα, 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 HP1aα, CTCF, AGO1, RNAPII and histone marks around regulated exons and can differentiate patterns of skipping and inclusion. Additionally, we found a significant association of HP1aα and CTCF activities around the regulated exons and a putative DNA binding site for HP1aα. Conclusions: Our results show that a considerable number of alternative splicing events could have a chromatin-dependent regulation involving the association of HP1aα and CTCF near regulated exons. Additionally, we find further evidence for the involvement of HP1aα and AGO1 in chromatin-related splicing regulation.
Fil: Agirre, Eneritz. Universitat Pompeu Fabra; España. Centre National de la Recherche Scientifique; Francia. Institute of Human Genetics; Francia
Fil: Bellora, Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Instituto de Investigaciones en Biodiversidad y Medioambiente. Universidad Nacional del Comahue. Centro Regional Universidad Bariloche. Instituto de Investigaciones en Biodiversidad y Medioambiente; Argentina. Universitat Pompeu Fabra; España
Fil: Alló, Mariano. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina. European Molecular Biology Laboratory; Alemania
Fil: Pagès, Amadís. Universitat Pompeu Fabra; España
Fil: Bertucci, Paola Yanina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina. European Molecular Biology Laboratory; Alemania
Fil: Kornblihtt, Alberto Rodolfo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina
Fil: Eyras, Eduardo. Universitat Pompeu Fabra; España. Institució Catalana de Recerca i Estudis Avancats; España
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, HP1aα, 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 HP1aα, CTCF, AGO1, RNAPII and histone marks around regulated exons and can differentiate patterns of skipping and inclusion. Additionally, we found a significant association of HP1aα and CTCF activities around the regulated exons and a putative DNA binding site for HP1aα. Conclusions: Our results show that a considerable number of alternative splicing events could have a chromatin-dependent regulation involving the association of HP1aα and CTCF near regulated exons. Additionally, we find further evidence for the involvement of HP1aα and AGO1 in chromatin-related splicing regulation.
publishDate 2015
dc.date.none.fl_str_mv 2015-12-02
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/85531
Agirre, Eneritz; Bellora, Nicolás; Alló, Mariano; Pagès, Amadís; Bertucci, Paola Yanina; et al.; A chromatin code for alternative splicing involving a putative association between CTCF and HP1aα proteins; BioMed Central; Bmc Biology; 13; 1; 2-12-2015; 1-14
1741-7007
CONICET Digital
CONICET
url http://hdl.handle.net/11336/85531
identifier_str_mv Agirre, Eneritz; Bellora, Nicolás; Alló, Mariano; Pagès, Amadís; Bertucci, Paola Yanina; et al.; A chromatin code for alternative splicing involving a putative association between CTCF and HP1aα proteins; BioMed Central; Bmc Biology; 13; 1; 2-12-2015; 1-14
1741-7007
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1186/s12915-015-0141-5
info:eu-repo/semantics/altIdentifier/url/https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-015-0141-5
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
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:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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