| http://purl.uniprot.org/citations/19103607 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/19103607 | http://www.w3.org/2000/01/rdf-schema#comment | "AimsThe transcription factor early growth response-1 (Egr-1) is increased in models of cardiac pathology; however, it is unclear how Egr-1 impacts the heart. We sought to identify how Egr-1 regulates expression of proteins involved in cardiomyocyte calcium homeostasis.MethodsProtein expression was measured by immunoblotting in control cardiac differentiated H9c2 cells or in H9c2 cells overexpressing wild-type Egr-1 (Egr-1) or an Egr-1 (I293F) mutant. Microspectrofluorimetry of fura-2-loaded cells was used to study calcium dynamics. Chromatin immunoprecipitation with anti-Egr-1 antibody was used to identify Egr-1-associated DNA.ResultsCalsequestrin (CSQ) expression was reduced in Egr-1- and profoundly reduced in I293F-expressing cells. Calreticulin, triadin, sarcoendoplasmic reticulum ATPase 2a, phospholamban, and phosphoserine 16-phospholamban expression was unaffected. Calcium release from CSQ-dependent ryanodine-sensitive stores was reduced in Egr-1 and absent in I293F-expressing cells. In contrast, calcium release from calreticulin-dependent inositol 1,4,5-trisphosphate stores was unaffected. In vivo and in vitro chromatin immunoprecipitation demonstrated Egr-1 binding to the CSQ2 promoter. The Egr-1-binding region contains overlapping Egr-1, SP1, and nuclear factor of activated T-cells (NFAT) sites and a CpG island. Reciprocal immunoprecipitation coupled to immunoblots indicated Egr-1:NFAT3 binding was present in all cells lines. Treatment with cyclosporin A, inhibition of DNA methylation using 5-azadeoxycytidine, or inhibition of protein acetylation using sodium butyrate reduced CSQ expression.ConclusionOur data suggest that Egr-1:DNA binding at the promoter, DNA methylation, and protein acetylation are important in CSQ repression. Moreover, we demonstrate that a reduction in CSQ protein is associated with abnormal calcium dynamics. We conclude that Egr-1 acts as a transcriptional repressor at the CSQ promoter, resulting in downregulation of CSQ, the major calcium storage protein that links excitation-contraction coupling in the cardiac sarcoendoplasmic reticulum."xsd:string |
| http://purl.uniprot.org/citations/19103607 | http://purl.org/dc/terms/identifier | "doi:10.1093/cvr/cvn357"xsd:string |
| http://purl.uniprot.org/citations/19103607 | http://purl.uniprot.org/core/author | "Chalifour L.E."xsd:string |
| http://purl.uniprot.org/citations/19103607 | http://purl.uniprot.org/core/author | "Komarova S.V."xsd:string |
| http://purl.uniprot.org/citations/19103607 | http://purl.uniprot.org/core/author | "Kasneci A."xsd:string |
| http://purl.uniprot.org/citations/19103607 | http://purl.uniprot.org/core/author | "Kemeny-Suss N.M."xsd:string |
| http://purl.uniprot.org/citations/19103607 | http://purl.uniprot.org/core/date | "2009"xsd:gYear |
| http://purl.uniprot.org/citations/19103607 | http://purl.uniprot.org/core/name | "Cardiovasc Res"xsd:string |
| http://purl.uniprot.org/citations/19103607 | http://purl.uniprot.org/core/pages | "695-702"xsd:string |
| http://purl.uniprot.org/citations/19103607 | http://purl.uniprot.org/core/title | "Egr-1 negatively regulates calsequestrin expression and calcium dynamics in ventricular cells."xsd:string |
| http://purl.uniprot.org/citations/19103607 | http://purl.uniprot.org/core/volume | "81"xsd:string |
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