A chromatin code for alternative splicing involving a putative association between CTCF and HP1α proteins
| Autor: | Paola Y. Bertucci, Amadís Pagès, Nicolás Bellora, Alberto R. Kornblihtt, Eneritz Agirre, Eduardo Eyras, Mariano Alló |
|---|---|
| Jazyk: | angličtina |
| Předmět: |
CHROMATIN
CCCTC-Binding Factor Chromosomal Proteins Non-Histone Physiology Exonic splicing enhancer Plant Science Splicing Chromodomain purl.org/becyt/ford/1 [https] Histones Cromatina Exon Structural Biology Eukaryotic Initiation Factors Genetics Agricultural and Biological Sciences(all) SPLICING CODE Splicing code Bioquímica y Biología Molecular Chromatin Cell biology Argonaute Proteins RNA splicing SPLICING General Agricultural and Biological Sciences CIENCIAS NATURALES Y EXACTAS Protein Binding Research Article Biotechnology Molecular Sequence Data Biology General Biochemistry Genetics and Molecular Biology Cell Line Ciencias Biológicas Splicing factor Regulació genètica Humans Nucleotide Motifs purl.org/becyt/ford/1.6 [https] Ecology Evolution Behavior and Systematics Binding Sites Base Sequence Biochemistry Genetics and Molecular Biology(all) Alternative splicing Cell Biology HISTONES Repressor Proteins Alternative Splicing Chromobox Protein Homolog 5 CTCF RNA Developmental Biology |
| Zdroj: | Recercat. Dipósit de la Recerca de Catalunya instname CONICET Digital (CONICET) Consejo Nacional de Investigaciones Científicas y Técnicas instacron:CONICET BMC Biology |
| ISSN: | 1741-7007 |
| DOI: | 10.1186/s12915-015-0141-5 |
| Popis: | 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 |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|