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The human Cx40 promoter polymorphism -44G-->A differentially affects transcriptional regulation by Sp1 and GATA4.
Firouzi, Mehran; Bierhuizen, Marti F A; Kok, Bart; Teunissen, Birgit E J; Jansen, Anita T; Jongsma, Habo J; Groenewegen, W Antoinette.
Afiliación
  • Firouzi M; Department of Medical Physiology, University Medical Center Utrecht, Yalelaan 50, 3584 CM Utrecht, The Netherlands.
Biochim Biophys Acta ; 1759(10): 491-6, 2006 Oct.
Article en En | MEDLINE | ID: mdl-17050003
Expression of the tissue-specific gap junction protein connexin(Cx)40 is regulated by the interaction of ubiquitous and tissue-specific factors such as Sp1 and GATA4. Cardiac Cx40 expression is altered under pathological conditions such as atrial fibrillation. A human promoter polymorphism, a G-->A change at position -44 that has been associated with atrial-specific arrhythmias, is located between the TBE-NKE-Sp and GATA consensus transcription factor binding sites important for the regulation of the mouse Cx40 gene. The presence of the A-allele at position -44 in promoter-reporter constructs significantly reduces promoter activity. Using electrophoretic mobility shift assays and luciferase reporter assays in various cell types, we show that Sp1 and GATA4 are important regulators of human Cx40 gene transcription and that the -44 G-->A polymorphism negatively affects the promoter regulation by the transcription factors Sp1 and GATA4.
Asunto(s)
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Polimorfismo Genético / Regulación de la Expresión Génica / Factor de Transcripción Sp1 / Regiones Promotoras Genéticas / Conexinas / Factor de Transcripción GATA4 Límite: Animals / Humans Idioma: En Revista: Biochim Biophys Acta Año: 2006 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Países Bajos
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Polimorfismo Genético / Regulación de la Expresión Génica / Factor de Transcripción Sp1 / Regiones Promotoras Genéticas / Conexinas / Factor de Transcripción GATA4 Límite: Animals / Humans Idioma: En Revista: Biochim Biophys Acta Año: 2006 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Países Bajos