Nucleic Acids Research, Vol 26, Issue 4 1092-1098, Copyright © 1998 by Oxford University Press
DL Baker, V Dave, T Reed, S Misra and M Periasamy
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.
ARTICLES
A novel E box/AT-rich element is required for muscle-specific expression of the sarcoplasmic reticulum Ca2+-ATPase (SERCA2) gene
Division of Cardiology, University of Cincinnati College of Medicine, ML542, 231 Bethesda Avenue, Cincinnati, OH 45267, USA.
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