Els factors GATA4 i GATA5 en la regulació transcripcional del gen que codifica pel canal de sodi cardíac (SCN5A)

The SCN5A gene encodes the alpha subunit of the cardiac sodium channel (NaV1.5), which is responsible for the influx of sodium ions through membrane of cardiomyocytes. Different evidences suggest that an aberrant expression of the SCN5A gene may cause cardiac arrhythmias. However, the mechanisms tha...

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Detalles Bibliográficos
Autor: Tarradas Pou, Anna
Tipo de recurso: tesis doctoral
Estado:Versión publicada
Fecha de publicación:2017
País:España
Institución:CBUC, CESCA
Repositorio:TDR. Tesis Doctorales en Red
OAI Identifier:oai:www.tdx.cat:10803/405732
Acceso en línea:http://hdl.handle.net/10803/405732
http://mediaserver.csuc.cat/tdx/documents/10/38/39/103839671496203440788452791945964211836/
http://mediaserver.csuc.cat/tdx/documents/19/30/10/19301035926491042153613328926235842236/
Access Level:acceso abierto
Palabra clave:Regulació transcripcional
Regulación transcripcional
Transcriptional regulation
Expressió gènica
Expresión génica
Gene expression
Factors GATA
Factores GATA
GATA factors
SCN5A
Canals iònics
Canales iónicos
Ion channels
Arítmia cardíaca
Arritmia cardíaca
Cardiac arrhythmia
575
Descripción
Sumario:The SCN5A gene encodes the alpha subunit of the cardiac sodium channel (NaV1.5), which is responsible for the influx of sodium ions through membrane of cardiomyocytes. Different evidences suggest that an aberrant expression of the SCN5A gene may cause cardiac arrhythmias. However, the mechanisms that control SCN5A expression regulation are largely unknown. This thesis proposes a new mechanism of SCN5A transcriptional regulation in the adult human heart: transcription factors GATA4 and GATA5 synergize in the activation of the SCN5A expression. In addition, it has been proposed that GATA4 activity on the SCN5A is regulated by acetylation/deacetylation via the acetyltransferase p300 and the deacetylase HDAC2. It has been identified three lysines of GATA4 that are targets of p300 and HDAC2. In summary, this study contributes to further understand the molecular basis of the cardiac arrhythmias associated with alteration of sodium currents