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- W8363805 abstract "The sarco(endo)plasmic reticulum Ca2+-ATPases belong to a family of active calcium transport enzymes encoded by 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 alternative splicing the cardiac/slow-twitch muscle specific SERCA2a isoform and the ubiquitous SERCA2b isoform. The sequence of the proximal 225 bp region of the SERCA2 genes is 80% G+C-rich, is highly conserved among human, rabbit, rat and mouse species, and 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 other two 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 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 −1.7kb 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 that the region from −225 to −1232 bp contains regulatory DNA elements which modulate negatively the expression of the SERCA2 in neonatal cardiomyocytes, suggesting that this region might be important during cardiac hypertrophy and in response to hormonal and metabolic signals. Taken together, these findings suggest that the entire functional 5′-regulatory region of the SERCA2 gene is confined within 1.5 kb of upstream from the transcription initiation site." @default.
- W8363805 created "2016-06-24" @default.
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- W8363805 date "2003-01-01" @default.
- W8363805 modified "2023-10-02" @default.
- W8363805 title "The SERCA2 gene: genomic organization and promoter characterization" @default.
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- W8363805 doi "https://doi.org/10.1007/978-1-4615-0347-7_35" @default.
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