Articles producció científica> Ciències Mèdiques Bàsiques

Epigenetic Changes Governing Scn5a Expression in Denervated Skeletal Muscle

  • Identification data

    Identifier: imarina:9178046
    Authors:
    Carreras, DavidMartinez-Moreno, RebeccaPinsach-Abuin, Mel LinaSantafe, Manel M.Goma, PolBrugada, RamonScornik, Fabiana S.Perez, Guillermo J.Pagans, Sara
    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.
  • Others:

    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
  • Keywords:

    Biochemistry & Molecular Biology,Catalysis,Chemistry, Multidisciplinary,Computer Science Applications,Inorganic Chemistry,Medicine (Miscellaneous),Molecular Biology,Organic Chemistry,Physical and Theoretical Chemistry,Spectroscopy
    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
    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
    B
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