Neuronal cell depolarization induces intragenic chromatin modifications affecting NCAM alternative splicing
In search for physiological pathways affecting alternative splicing through its kinetic coupling with transcription, we found that membrane depolarization of neuronal cells triggers the skipping of exon 18 from the neural cell adhesion molecule (NCAM) mRNA, independently of the calcium/calmodulin pr...
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2009
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00278424_v106_n11_p4325_Schor http://hdl.handle.net/20.500.12110/paper_00278424_v106_n11_p4325_Schor |
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paper:paper_00278424_v106_n11_p4325_Schor2023-06-08T14:54:22Z Neuronal cell depolarization induces intragenic chromatin modifications affecting NCAM alternative splicing Histone acetylation MRNA processing Neuronal excitation Transcription calcium calmodulin dependent protein kinase messenger RNA nerve cell adhesion molecule RNA polymerase II trichostatin A acetylation alternative RNA splicing animal cell article cell differentiation cell elongation cell function cell membrane depolarization chromatin chromatin structure controlled study embryo exon gene location genetic epigenesis methylation mutant nerve cell nonhuman priority journal promoter region protein folding rat RNA splicing transcription initiation Acetylation Alternative Splicing Animals Chromatin Epigenesis, Genetic Exons Histones Membrane Potentials Neural Cell Adhesion Molecules Neurons Rats RNA Polymerase II In search for physiological pathways affecting alternative splicing through its kinetic coupling with transcription, we found that membrane depolarization of neuronal cells triggers the skipping of exon 18 from the neural cell adhesion molecule (NCAM) mRNA, independently of the calcium/calmodulin protein kinase IV pathway. We show that this exon responds to RNA polymerase II elongation, because its inclusion is increased by a slow polymerase II mutant. Depolarization affects the chromatin template in a specific way, by causing H3K9 hyper-acetylation restricted to an internal region of the NCAM gene surrounding the alternative exon. This intragenic histone hyper-acetylation is not paralleled by acetylation at the promoter, is associated with chromatin relaxation, and is linked to H3K36 trimethylation. The effects on acetylation and splicing fully revert when the depolarizing conditions are withdrawn and can be both duplicated and potentiated by the histone deacetylase inhibitor trichostatin A. Our results are consistent with a mechanism involving the kinetic coupling of splicing and transcription in response to depolarization through intragenic epigenetic changes on a gene that is relevant for the differentiation and function of neuronal cells. 2009 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00278424_v106_n11_p4325_Schor http://hdl.handle.net/20.500.12110/paper_00278424_v106_n11_p4325_Schor |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Histone acetylation MRNA processing Neuronal excitation Transcription calcium calmodulin dependent protein kinase messenger RNA nerve cell adhesion molecule RNA polymerase II trichostatin A acetylation alternative RNA splicing animal cell article cell differentiation cell elongation cell function cell membrane depolarization chromatin chromatin structure controlled study embryo exon gene location genetic epigenesis methylation mutant nerve cell nonhuman priority journal promoter region protein folding rat RNA splicing transcription initiation Acetylation Alternative Splicing Animals Chromatin Epigenesis, Genetic Exons Histones Membrane Potentials Neural Cell Adhesion Molecules Neurons Rats RNA Polymerase II |
| spellingShingle |
Histone acetylation MRNA processing Neuronal excitation Transcription calcium calmodulin dependent protein kinase messenger RNA nerve cell adhesion molecule RNA polymerase II trichostatin A acetylation alternative RNA splicing animal cell article cell differentiation cell elongation cell function cell membrane depolarization chromatin chromatin structure controlled study embryo exon gene location genetic epigenesis methylation mutant nerve cell nonhuman priority journal promoter region protein folding rat RNA splicing transcription initiation Acetylation Alternative Splicing Animals Chromatin Epigenesis, Genetic Exons Histones Membrane Potentials Neural Cell Adhesion Molecules Neurons Rats RNA Polymerase II Neuronal cell depolarization induces intragenic chromatin modifications affecting NCAM alternative splicing |
| topic_facet |
Histone acetylation MRNA processing Neuronal excitation Transcription calcium calmodulin dependent protein kinase messenger RNA nerve cell adhesion molecule RNA polymerase II trichostatin A acetylation alternative RNA splicing animal cell article cell differentiation cell elongation cell function cell membrane depolarization chromatin chromatin structure controlled study embryo exon gene location genetic epigenesis methylation mutant nerve cell nonhuman priority journal promoter region protein folding rat RNA splicing transcription initiation Acetylation Alternative Splicing Animals Chromatin Epigenesis, Genetic Exons Histones Membrane Potentials Neural Cell Adhesion Molecules Neurons Rats RNA Polymerase II |
| description |
In search for physiological pathways affecting alternative splicing through its kinetic coupling with transcription, we found that membrane depolarization of neuronal cells triggers the skipping of exon 18 from the neural cell adhesion molecule (NCAM) mRNA, independently of the calcium/calmodulin protein kinase IV pathway. We show that this exon responds to RNA polymerase II elongation, because its inclusion is increased by a slow polymerase II mutant. Depolarization affects the chromatin template in a specific way, by causing H3K9 hyper-acetylation restricted to an internal region of the NCAM gene surrounding the alternative exon. This intragenic histone hyper-acetylation is not paralleled by acetylation at the promoter, is associated with chromatin relaxation, and is linked to H3K36 trimethylation. The effects on acetylation and splicing fully revert when the depolarizing conditions are withdrawn and can be both duplicated and potentiated by the histone deacetylase inhibitor trichostatin A. Our results are consistent with a mechanism involving the kinetic coupling of splicing and transcription in response to depolarization through intragenic epigenetic changes on a gene that is relevant for the differentiation and function of neuronal cells. |
| title |
Neuronal cell depolarization induces intragenic chromatin modifications affecting NCAM alternative splicing |
| title_short |
Neuronal cell depolarization induces intragenic chromatin modifications affecting NCAM alternative splicing |
| title_full |
Neuronal cell depolarization induces intragenic chromatin modifications affecting NCAM alternative splicing |
| title_fullStr |
Neuronal cell depolarization induces intragenic chromatin modifications affecting NCAM alternative splicing |
| title_full_unstemmed |
Neuronal cell depolarization induces intragenic chromatin modifications affecting NCAM alternative splicing |
| title_sort |
neuronal cell depolarization induces intragenic chromatin modifications affecting ncam alternative splicing |
| publishDate |
2009 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00278424_v106_n11_p4325_Schor http://hdl.handle.net/20.500.12110/paper_00278424_v106_n11_p4325_Schor |
| _version_ |
1768543548051816448 |