title: Identification of functional corticosteroid response elements involved in regulation of Cacna1g expression in cardiac myocytes.
abstract: We recently reported that corticosteroids increase the expression of the T-type channel Ca(v)3.1 through a transcriptional up-regulation of the Ca(v)3.1 encoding gene cacna1g. The nucleotide sequence analysis of cacna1g promoter revealed putative glucocorticoid response elements (GREs). However, the functional GREs involved in the regulation of cacna1g expression in neonatal cardiac myocytes are unknown. In the present study we have investigated the nuclear targets responsible for the transcriptional regulation of cacna1g. We identified five GREs from the nucleotide sequence of cacna1g promoter. Additionally, using punctual mutagenesis approach, three functional categories of GREs have been identified: (i) GRE-1 involved in promoter activity induced by aldosterone (Aldo, 1 microM); (ii) GRE-4 and GRE-5 involved in promoter activity induced by dexamethasone (Dex, 1 microM); and (iii) GRE-2 and GRE-3 involved in the basal level of neonatal promoter activity. The data presented here lead to better understanding of the molecular mechanisms underlying the regulation of Ca(v)3.1 channel expression by corticosteroids. These new findings have attractive physiological features during cardiac development and pathology such as arrhythmias.
authors.affiliation: CNRS UMR 8162, Université Paris-Sud XI, Hôpital Marie Lannelongue, 133 Avenue de la Résistance, 92350 Le Plessis Robinson, France. fatima.ben-mohamed@inserm.fr
authors.forename: Fatima
authors.initials: F
authors.lastname: BenMohamed
authors.forename: Yann
authors.initials: Y
authors.lastname: Ruchon
authors.forename: Véronique
authors.initials: V
authors.lastname: Capuano
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Renaud
mesh_terms: D000305:Adrenal Cortex Hormones / Q000494:pharmacology; D000450:Aldosterone / Q000494:pharmacology*; D000818:Animals; D020747:Calcium Channels, T-Type / Q000235:genetics* / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D005786:Gene Expression Regulation; D005938:Glucocorticoids / Q000494:pharmacology*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D051381:Rats; D017208:Rats, Wistar; D020218:Response Elements / Q000235:genetics*
chemical_list: D000305:Adrenal Cortex Hormones; C500994:Cacna1g protein, rat; D020747:Calcium Channels, T-Type; D005938:Glucocorticoids; D000450:Aldosterone; D003907:Dexamethasone
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