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Article: Molecular cloning and analysis of the human cardiac sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA2) gene promoter

TitleMolecular cloning and analysis of the human cardiac sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA2) gene promoter
Authors
Issue Date1996
Citation
Journal of Molecular and Cellular Cardiology, 1996, v. 28 n. 10, p. 2139-2150 How to Cite?
AbstractThe sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA2) plays a critical role in regulating Ca2+ movements in myocardium. In cardiac hypertrophy and human heart failure, the decrease in mRNA and protein levels of SERCA2 might account for the reduced diastolic Ca2+ re-uptake seen in these conditions. To investigate the regulation of human SERCA2 gene expression, an 18.6-kb human genomic clone that contains exons 1, 2 and 3 of the SERCA2 gene has been isolated, and 13 kb of 5' upstream flanking sequence of which the proximal 2.5 kb of the promoter have been sequenced. Similar to the rabbit gene, the human SERCA2 promoter possesses a TATA-like box (-25 bp), a CAAT-box (-78 bp) and a number of consensus cis-regulatory elements including three Sp1 sites, a CACCC-box, and an OTF-1 binding sequence. No CArG box (present in the rabbit SERCA2 promoter) was identified in the human proximal promoter. Two putative thyroid response elements (TRE) are also present, suggesting that the human SERCA2 gene is also regulated by thyroid hormone as are the rat and rabbit genes. To study transcriptional activity of the human SERCA2 promoter in vitro, luciferase reporter plasmids containing a series of 5' deleted promoter constructs from -2577 bp to +170 bp were transfected into neonatal rat cardiomyocytes and C2C12 myotubes. The results suggest that: (a) the sequences from the transcription start site to -263 bp are necessary to obtain maximal transcriptional activity; (b) sequences from the transcription start site to -125 bp are essential for basal transcriptional activity; (c) at least one positive regulatory element is located between -263 bp and -125 bp; and (d) at least one negative regulatory element is present between -1741 bp and -412 bp.
Persistent Identifierhttp://hdl.handle.net/10722/195241
ISSN
2015 Impact Factor: 4.874
2015 SCImago Journal Rankings: 2.522
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorWankerl, M-
dc.contributor.authorBoheler, KR-
dc.contributor.authorFiszman, MY-
dc.contributor.authorSchwartz, K-
dc.date.accessioned2014-02-25T01:40:20Z-
dc.date.available2014-02-25T01:40:20Z-
dc.date.issued1996-
dc.identifier.citationJournal of Molecular and Cellular Cardiology, 1996, v. 28 n. 10, p. 2139-2150-
dc.identifier.issn0022-2828-
dc.identifier.urihttp://hdl.handle.net/10722/195241-
dc.description.abstractThe sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA2) plays a critical role in regulating Ca2+ movements in myocardium. In cardiac hypertrophy and human heart failure, the decrease in mRNA and protein levels of SERCA2 might account for the reduced diastolic Ca2+ re-uptake seen in these conditions. To investigate the regulation of human SERCA2 gene expression, an 18.6-kb human genomic clone that contains exons 1, 2 and 3 of the SERCA2 gene has been isolated, and 13 kb of 5' upstream flanking sequence of which the proximal 2.5 kb of the promoter have been sequenced. Similar to the rabbit gene, the human SERCA2 promoter possesses a TATA-like box (-25 bp), a CAAT-box (-78 bp) and a number of consensus cis-regulatory elements including three Sp1 sites, a CACCC-box, and an OTF-1 binding sequence. No CArG box (present in the rabbit SERCA2 promoter) was identified in the human proximal promoter. Two putative thyroid response elements (TRE) are also present, suggesting that the human SERCA2 gene is also regulated by thyroid hormone as are the rat and rabbit genes. To study transcriptional activity of the human SERCA2 promoter in vitro, luciferase reporter plasmids containing a series of 5' deleted promoter constructs from -2577 bp to +170 bp were transfected into neonatal rat cardiomyocytes and C2C12 myotubes. The results suggest that: (a) the sequences from the transcription start site to -263 bp are necessary to obtain maximal transcriptional activity; (b) sequences from the transcription start site to -125 bp are essential for basal transcriptional activity; (c) at least one positive regulatory element is located between -263 bp and -125 bp; and (d) at least one negative regulatory element is present between -1741 bp and -412 bp.-
dc.languageeng-
dc.relation.ispartofJournal of Molecular and Cellular Cardiology-
dc.titleMolecular cloning and analysis of the human cardiac sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA2) gene promoter-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1006/jmcc.1996.0206-
dc.identifier.pmid8930809-
dc.identifier.scopuseid_2-s2.0-0030271606-
dc.identifier.volume28-
dc.identifier.issue10-
dc.identifier.spage2139-
dc.identifier.epage2150-
dc.identifier.isiWOS:A1996VQ28800008-

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