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Abstract:

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. © 2015 Agirre et al.; licensee BioMed Central.

Registro:

Documento: Artículo
Título:A chromatin code for alternative splicing involving a putative association between CTCF and HP1aα proteins
Autor:Agirre, E.; Bellora, N.; Alló, M.; Pagès, A.; Bertucci, P.; Kornblihtt, A.R.; Eyras, E.
Filiación:Universitat Pompeu Fabra, Barcelona, E08003, Spain
IFIBYNE-UBA-CONICET, Departamento de Fisiología, Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, (C1428EHA), Buenos Aires, Argentina
Centre for Genomic Regulation, Barcelona, E08003, Spain
Catalan Institution of Research and Advanced Studies (ICREA), Barcelona, E08010, Spain
Institute of Human Genetics, CNRS UPR 1142, Montpellier, France
INIBIOMA, CONICET-UNComahue, Bariloche, Río Negro, Argentina
European Molecular Biology Laboratory, Meyerhofstrasse 1, Heidelberg, 69117, Germany
Palabras clave:Chromatin; Histones; Splicing; Splicing code; argonaute protein; CCCTC-binding factor; chromatin; EIF2C1 protein, human; heterochromatin-specific nonhistone chromosomal protein HP-1; initiation factor; nonhistone protein; protein binding; repressor protein; RNA; alternative RNA splicing; binding site; cell line; chromatin; genetics; human; metabolism; molecular genetics; nucleotide motif; nucleotide sequence; Alternative Splicing; Argonaute Proteins; Base Sequence; Binding Sites; Cell Line; Chromatin; Chromosomal Proteins, Non-Histone; Eukaryotic Initiation Factors; Humans; Molecular Sequence Data; Nucleotide Motifs; Protein Binding; Repressor Proteins; RNA
Año:2015
Volumen:13
Número:1
DOI: http://dx.doi.org/10.1186/s12915-015-0141-5
Título revista:BMC Biology
Título revista abreviado:BMC Biol.
ISSN:17417007
CAS:RNA, 63231-63-0; Argonaute Proteins; CCCTC-binding factor; Chromatin; Chromosomal Proteins, Non-Histone; EIF2C1 protein, human; Eukaryotic Initiation Factors; heterochromatin-specific nonhistone chromosomal protein HP-1; Repressor Proteins; RNA
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_17417007_v13_n1_p_Agirre

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Citas:

---------- APA ----------
Agirre, E., Bellora, N., Alló, M., Pagès, A., Bertucci, P., Kornblihtt, A.R. & Eyras, E. (2015) . A chromatin code for alternative splicing involving a putative association between CTCF and HP1aα proteins. BMC Biology, 13(1).
http://dx.doi.org/10.1186/s12915-015-0141-5
---------- CHICAGO ----------
Agirre, E., Bellora, N., Alló, M., Pagès, A., Bertucci, P., Kornblihtt, A.R., et al. "A chromatin code for alternative splicing involving a putative association between CTCF and HP1aα proteins" . BMC Biology 13, no. 1 (2015).
http://dx.doi.org/10.1186/s12915-015-0141-5
---------- MLA ----------
Agirre, E., Bellora, N., Alló, M., Pagès, A., Bertucci, P., Kornblihtt, A.R., et al. "A chromatin code for alternative splicing involving a putative association between CTCF and HP1aα proteins" . BMC Biology, vol. 13, no. 1, 2015.
http://dx.doi.org/10.1186/s12915-015-0141-5
---------- VANCOUVER ----------
Agirre, E., Bellora, N., Alló, M., Pagès, A., Bertucci, P., Kornblihtt, A.R., et al. A chromatin code for alternative splicing involving a putative association between CTCF and HP1aα proteins. BMC Biol. 2015;13(1).
http://dx.doi.org/10.1186/s12915-015-0141-5