Epigenetic Changes Governing Scn5a Expression in Denervated Skeletal Muscle
| Autor: | Manel M. Santafé, Mel·lina Pinsach-Abuin, Rebecca Martinez-Moreno, Guillermo J. Pérez, Sara Pagans, Ramon Brugada, David Carreras, Pol Gomà, Fabiana S. Scornik |
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| Rok vydání: | 2021 |
| Předmět: |
Male
epigenetic mechanisms Scn5a Epigenesis Genetic NAV1.5 Voltage-Gated Sodium Channel lcsh:Chemistry Rats Sprague-Dawley Transcriptome Transcriptional regulation transcriptional regulation RNA-Seq lcsh:QH301-705.5 Spectroscopy Denervation histone modifications GATA4 Cardiac action potential General Medicine Muscle Denervation Computer Science Applications Cell biology medicine.anatomical_structure cardiac arrhythmias cardiovascular system Epigenetics Arrhythmia Gene isoform congenital hereditary and neonatal diseases and abnormalities Arrítmia Biology Response Elements Article Catalysis Inorganic Chemistry Cor -- Malalties Cor -- Malalties -- Aspectes genètics skeletal muscle denervation medicine Animals cardiovascular diseases Physical and Theoretical Chemistry Muscle Skeletal Molecular Biology Transcription factor Organic Chemistry Skeletal muscle Heart -- Diseases -- Genetic aspects Heart -- Diseases Epigenètica GATA4 Transcription Factor Rats lcsh:Biology (General) lcsh:QD1-999 H3K27 acetylation |
| Zdroj: | International Journal of Molecular Sciences, 2021, vol. 22, núm. 5, p. 2755 Articles publicats (D-CM) Carreras, David Martínez Moreno, Rebecca Pinsach Abuin, Mel·lina Santafe, Manel M. Gomà, Pol Brugada, Ramon Scornik, Fabiana S. Pérez González, Guillermo J. Sara Pagans 2021 Epigenetic Changes Governing Scn5a Expression in Denervated Skeletal Muscle International Journal of Molecular Sciences 22 5 2755 DUGiDocs – Universitat de Girona instname International Journal of Molecular Sciences Volume 22 Issue 5 International Journal of Molecular Sciences, Vol 22, Iss 2755, p 2755 (2021) |
| Popis: | The SCN5A gene encodes the α-subunit of the voltage-gated cardiac sodium channel (NaV1.5), a key player in cardiac action potential depolarization. Genetic variants in protein-coding regions of the human SCN5A have been largely associated with inherited cardiac arrhythmias. Increasing evidence also suggests that aberrant expression of the SCN5A gene could increase susceptibility to arrhythmogenic diseases, but the mechanisms governing SCN5A expression are not yet well understood. To gain insights into the molecular basis of SCN5A gene regulation, we used rat gastrocnemius muscle four days following denervation, a process well known to stimulate Scn5a expression. Our results show that denervation of rat skeletal muscle induces the expression of the adult cardiac Scn5a isoform. RNA-seq experiments reveal that denervation leads to significant changes in the transcriptome, with Scn5a amongst the fifty top upregulated genes. Consistent with this increase in expression, ChIP-qPCR assays show enrichment of H3K27ac and H3K4me3 and binding of the transcription factor Gata4 near the Scn5a promoter region. Also, Gata4 mRNA levels are significantly induced upon denervation. Genome-wide analysis of H3K27ac by ChIP-seq suggest that a super enhancer recently described to regulate Scn5a in cardiac tissue is activated in response to denervation. Altogether, our experiments reveal that similar mechanisms regulate the expression of Scn5a in denervated muscle and cardiac tissue, suggesting a conserved pathway for SCN5A expression among striated muscles This research was funded by the University of Girona, grant number MPCUdG2016/039 and Obra Social La Caixa. D.C. acknowledges a predoctoral fellowship from the Agència de Gesitó d’Ajusts Universitaris I de Recerca-Generalitat de Catalunya (2018FI_B00969) and European Social Fund (ESF) |
| Databáze: | OpenAIRE |
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