Sarco(endo)plasmic Reticulum Ca2+-ATPase-2 Gene: Structure and Transcriptional Regulation of the Human Gene
The sarco(endo)plasmic reticulum Ca2+-ATPases (SERCAs) belong to a family of active calcium transport enzymes encoded by the SERCA1, 2, and 3 genes. In this study, we describe the complete structure of the human SERCA2 gene and its 5’ -regulatory region. The hSERCA2 gene is located in chromosome 12...
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Wiley
2002-01-01
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| Series: | The Scientific World Journal |
| Online Access: | http://dx.doi.org/10.1100/tsw.2002.228 |
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| author | Angel Zarain-Herzberg Georgina Alvarez-Fernandez |
| author_facet | Angel Zarain-Herzberg Georgina Alvarez-Fernandez |
| author_sort | Angel Zarain-Herzberg |
| collection | DOAJ |
| description | The sarco(endo)plasmic reticulum Ca2+-ATPases (SERCAs) belong to a family of active calcium transport enzymes encoded by the SERCA1, 2, and 3 genes. In this study, we describe the complete structure of the human SERCA2 gene and its 5’ -regulatory region. The hSERCA2 gene is located in chromosome 12 position q24.1 in Contig NT_009770.8, spans 70 kb, and is organized in 21 exons intervened by 20 introns. The last two exons of the pre-mRNA produce by alternatively splicing the cardiac/slow-twitch muscle-specific SERCA2a isoform and the ubiquitous SERCA2b isoform. The sequence of the proximal 225-bp regulatory region of the SERCA2 genes is 80% G+C-rich and is conserved among human, rabbit, rat, and mouse species. It contains a TATA-like-box, an E-box/USF sequence, a CAAT-box, four Sp1 binding sites, and a thyroid hormone responsive element (TRE). There are two other conserved regulatory regions located between positions -410 to -661 bp and from -919 to -1410 bp. Among the DNA cis-elements present in these two regulatory regions there are potential binding sites for: GATA-4, -5, -6, Nkx-2.5/Csx, OTF-1, USF, MEF-2, SRF, PPAR/RXR, AP-2, and TREs. Upstream from position -1.5 kb, there is no significant homology among the SERCA2 genes cloned. In addition, the human gene has several repeated sequences mainly of the Alu and L2 type located upstream from position -1.7 kb, spanning in a continuous fashion for more than 40 kb. In this study, we report the cloning of 2.4 kb of 5’-regulatory region and demonstrate that the proximal promoter region is sufficient for expression in cardiac myocytes, and the region from -225 to -1232 bp contains regulatory DNA elements which down-regulate the expression of the SERCA2 gene in neonatal cardiomyocytes. |
| format | Article |
| id | doaj-art-bb00b918c1464cd28c355a305d4e952c |
| institution | Kabale University |
| issn | 1537-744X |
| language | English |
| publishDate | 2002-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | The Scientific World Journal |
| spelling | doaj-art-bb00b918c1464cd28c355a305d4e952c2025-02-03T06:07:19ZengWileyThe Scientific World Journal1537-744X2002-01-0121469148310.1100/tsw.2002.228Sarco(endo)plasmic Reticulum Ca2+-ATPase-2 Gene: Structure and Transcriptional Regulation of the Human GeneAngel Zarain-Herzberg0Georgina Alvarez-Fernandez1Laboratorio de Biología Molecular, Departamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México, México DF. 04510, MexicoLaboratorio de Biología Molecular, Departamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México, México DF. 04510, MexicoThe sarco(endo)plasmic reticulum Ca2+-ATPases (SERCAs) belong to a family of active calcium transport enzymes encoded by the SERCA1, 2, and 3 genes. In this study, we describe the complete structure of the human SERCA2 gene and its 5’ -regulatory region. The hSERCA2 gene is located in chromosome 12 position q24.1 in Contig NT_009770.8, spans 70 kb, and is organized in 21 exons intervened by 20 introns. The last two exons of the pre-mRNA produce by alternatively splicing the cardiac/slow-twitch muscle-specific SERCA2a isoform and the ubiquitous SERCA2b isoform. The sequence of the proximal 225-bp regulatory region of the SERCA2 genes is 80% G+C-rich and is conserved among human, rabbit, rat, and mouse species. It contains a TATA-like-box, an E-box/USF sequence, a CAAT-box, four Sp1 binding sites, and a thyroid hormone responsive element (TRE). There are two other conserved regulatory regions located between positions -410 to -661 bp and from -919 to -1410 bp. Among the DNA cis-elements present in these two regulatory regions there are potential binding sites for: GATA-4, -5, -6, Nkx-2.5/Csx, OTF-1, USF, MEF-2, SRF, PPAR/RXR, AP-2, and TREs. Upstream from position -1.5 kb, there is no significant homology among the SERCA2 genes cloned. In addition, the human gene has several repeated sequences mainly of the Alu and L2 type located upstream from position -1.7 kb, spanning in a continuous fashion for more than 40 kb. In this study, we report the cloning of 2.4 kb of 5’-regulatory region and demonstrate that the proximal promoter region is sufficient for expression in cardiac myocytes, and the region from -225 to -1232 bp contains regulatory DNA elements which down-regulate the expression of the SERCA2 gene in neonatal cardiomyocytes.http://dx.doi.org/10.1100/tsw.2002.228 |
| spellingShingle | Angel Zarain-Herzberg Georgina Alvarez-Fernandez Sarco(endo)plasmic Reticulum Ca2+-ATPase-2 Gene: Structure and Transcriptional Regulation of the Human Gene The Scientific World Journal |
| title | Sarco(endo)plasmic Reticulum Ca2+-ATPase-2 Gene: Structure and Transcriptional Regulation of the Human Gene |
| title_full | Sarco(endo)plasmic Reticulum Ca2+-ATPase-2 Gene: Structure and Transcriptional Regulation of the Human Gene |
| title_fullStr | Sarco(endo)plasmic Reticulum Ca2+-ATPase-2 Gene: Structure and Transcriptional Regulation of the Human Gene |
| title_full_unstemmed | Sarco(endo)plasmic Reticulum Ca2+-ATPase-2 Gene: Structure and Transcriptional Regulation of the Human Gene |
| title_short | Sarco(endo)plasmic Reticulum Ca2+-ATPase-2 Gene: Structure and Transcriptional Regulation of the Human Gene |
| title_sort | sarco endo plasmic reticulum ca2 atpase 2 gene structure and transcriptional regulation of the human gene |
| url | http://dx.doi.org/10.1100/tsw.2002.228 |
| work_keys_str_mv | AT angelzarainherzberg sarcoendoplasmicreticulumca2atpase2genestructureandtranscriptionalregulationofthehumangene AT georginaalvarezfernandez sarcoendoplasmicreticulumca2atpase2genestructureandtranscriptionalregulationofthehumangene |