title: The human Cx40 promoter polymorphism -44G-->A differentially affects transcriptional regulation by Sp1 and GATA4.
abstract: 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.
authors.affiliation: Department of Medical Physiology, University Medical Center Utrecht, Yalelaan 50, 3584 CM Utrecht, The Netherlands.
authors.forename: Mehran
authors.initials: M
authors.lastname: Firouzi
authors.forename: Marti F A
authors.initials: MF
authors.lastname: Bierhuizen
authors.forename: Bart
authors.initials: B
authors.lastname: Kok
authors.forename: Birgit E J
authors.initials: BE
authors.lastname: Teunissen
authors.forename: Anita T
authors.initials: AT
authors.lastname: Jansen
authors.forename: Habo J
authors.initials: HJ
authors.lastname: Jongsma
authors.forename: W Antoinette
authors.initials: WA
authors.lastname: Groenewegen
mesh_terms: D000818:Animals; D001483:Base Sequence; D017630:Connexins / Q000235:genetics*; D017931:DNA Primers; D050991:GATA4 Transcription Factor / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D051379:Mice; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D016329:Sp1 Transcription Factor / Q000502:physiology*; D000097003:Gap Junction alpha-5 Protein
chemical_list: D017630:Connexins; D017931:DNA Primers; D050991:GATA4 Transcription Factor; D016329:Sp1 Transcription Factor; D000097003:Gap Junction alpha-5 Protein; C484170:GATA4 protein, human