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M W McBurney L C Sutherland C N Adra B Leclair M A Rudnicki K Jardine 《Nucleic acids research》1991,19(20):5755-5761
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A novel E box/AT-rich element is required for muscle-specific expression of the sarcoplasmic reticulum Ca2+-ATPase (SERCA2) gene.
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The cardiac/slow twitch sarcoplasmic reticulum (SR) Ca2+-ATPase gene (SERCA2 ) encodes a calcium transport pump whose expression is regulated in a tissue- and development-specific manner. Previously we have identified two distinct positive regulatory regions (bp -284 to -72 and -1815 to -1105) as important for SERCA2 promoter activity. Here we demonstrate that the SERCA2 distal promoter region functions like an enhancer by activating a heterologous promoter (TK) in a muscle cell-specific manner. Through deletion analysis a core enhancer region was delimited to the -1467 to -1105 bp fragment. We identified the E box/AT-rich element located at -1115 bp as critical for maximal enhancer activity. Gel mobility shift studies revealed that this E box/AT-rich element specifically binds a protein which is induced during Sol8 myogenesis. This region includes two other cis -acting elements, CArG and MCAT, which also bind specific nuclear protein complexes from Sol8 myotubes. Mutagenesis of each of these sites resulted in decreased SERCA/TK-CAT promoter activity. Based on these data, we propose that the E box/AT-rich element may contribute along with CArG and MCAT elements to the overall activation and regulation of the SERCA2 gene promoter. 相似文献
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Upstream Stimulatory Factor Regulates Major Histocompatibility Complex Class I Gene Expression: the U2ΔE4 Splice Variant Abrogates E-Box Activity
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T. Kevin Howcroft Charles Murphy Jocelyn D. Weissman Sam J. Huber Michle Sawadogo Dinah S. Singer 《Molecular and cellular biology》1999,19(7):4788-4797