A chromatin code for alternative splicing involving a putative association between CTCF and HP1aα 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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2015
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_17417007_v13_n1_p_Agirre http://hdl.handle.net/20.500.12110/paper_17417007_v13_n1_p_Agirre |
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paper:paper_17417007_v13_n1_p_Agirre2023-06-08T16:27:00Z A chromatin code for alternative splicing involving a putative association between CTCF and HP1aα proteins Allo, Mariano Bertucci, Paola Yanina Kornblihtt, Alberto Rodolfo 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 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. Fil:Alló, M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Bertucci, P. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Kornblihtt, A.R. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2015 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_17417007_v13_n1_p_Agirre http://hdl.handle.net/20.500.12110/paper_17417007_v13_n1_p_Agirre |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
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 |
| spellingShingle |
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 Allo, Mariano Bertucci, Paola Yanina Kornblihtt, Alberto Rodolfo A chromatin code for alternative splicing involving a putative association between CTCF and HP1aα proteins |
| topic_facet |
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 |
| 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. © 2015 Agirre et al.; licensee BioMed Central. |
| author |
Allo, Mariano Bertucci, Paola Yanina Kornblihtt, Alberto Rodolfo |
| author_facet |
Allo, Mariano Bertucci, Paola Yanina Kornblihtt, Alberto Rodolfo |
| author_sort |
Allo, Mariano |
| title |
A chromatin code for alternative splicing involving a putative association between CTCF and HP1aα proteins |
| 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 |
chromatin code for alternative splicing involving a putative association between ctcf and hp1aα proteins |
| publishDate |
2015 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_17417007_v13_n1_p_Agirre http://hdl.handle.net/20.500.12110/paper_17417007_v13_n1_p_Agirre |
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1768544749305724928 |