Author, as appears in the article.: Carreras, David; Martinez-Moreno, Rebecca; Pinsach-Abuin, Mel Lina; Santafe, Manel M.; Goma, Pol; Brugada, Ramon; Scornik, Fabiana S.; Perez, Guillermo J.; Pagans, Sara;
Department: Ciències Mèdiques Bàsiques
URV's Author/s: Santafé Martínez, Manuel
Keywords: Upregulation Transcriptome Transcriptional regulation Transcription initiation Transcription factor gata 4 Sprague dawley rat Sodium channel nav1.5 Skeletal muscle denervation Skeletal muscle Scn5a protein, rat Scn5a Rna-seq Rna sequencing Response elements Rats, sprague-dawley Rats Rat Protein expression Promoter region Pathology Nonhuman Nav1.5 voltage-gated sodium channel Muscle, skeletal Muscle tissue Muscle denervation Metabolism Messenger rna Male Innervation Histone modifications Histone modification Histone h3 Heart tissue Heart arrhythmia H3k27 acetylation Genetics Genetic epigenesis Gene ontology Gene expression Gata4 transcription factor Gata4 protein, rat Gastrocnemius muscle Epigenetics Epigenetic mechanisms Epigenesis, genetic Enhancer region Dna responsive element Controlled study Chromatin immunoprecipitation sequencing Cardiac arrhythmias Biosynthesis Article Animals Animal tissue Animal model Animal experiment Animal Adult Acetylation
Abstract: The SCN5A gene encodes the alpha-subunit of the voltage-gated cardiac sodium channel (Na(V)1.5), 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.
Thematic Areas: Zootecnia / recursos pesqueiros Spectroscopy Saúde coletiva Química Psicología Physical and theoretical chemistry Organic chemistry Odontología Nutrição Molecular biology Medicine (miscellaneous) Medicina veterinaria Medicina iii Medicina ii Medicina i Materiais Interdisciplinar Inorganic chemistry Geociências Farmacia Engenharias iv Engenharias ii Engenharias i Educação física Computer science applications Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Ciências ambientais Ciências agrárias i Ciência de alimentos Ciência da computação Chemistry, multidisciplinary Catalysis Biotecnología Biodiversidade Biochemistry & molecular biology Astronomia / física
licence for use: https://creativecommons.org/licenses/by/3.0/es/
Author's mail: manuel.santafe@urv.cat
Author identifier: 0000-0002-5462-5108
Record's date: 2024-07-27
Papper version: info:eu-repo/semantics/publishedVersion
Link to the original source: https://www.mdpi.com/1422-0067/22/5/2755
Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
Papper original source: International Journal Of Molecular Sciences. 22 (5): 1-16
APA: Carreras, David; Martinez-Moreno, Rebecca; Pinsach-Abuin, Mel Lina; Santafe, Manel M.; Goma, Pol; Brugada, Ramon; Scornik, Fabiana S.; Perez, Guillerm (2021). Epigenetic Changes Governing Scn5a Expression in Denervated Skeletal Muscle. International Journal Of Molecular Sciences, 22(5), 1-16. DOI: 10.3390/ijms22052755
Article's DOI: 10.3390/ijms22052755
Entity: Universitat Rovira i Virgili
Journal publication year: 2021
Publication Type: Journal Publications