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Molecular and Cellular Biology, March 1999, p. 1841-1852, Vol. 19, No. 3
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

A Low-Affinity Serum Response Element Allows Other Transcription Factors To Activate Inducible Gene Expression in Cardiac Myocytes

Wirt A. Hines,1 Jacqueline Thorburn,2 and Andrew Thorburn2,*

Department of Human Genetics,1 Huntsman Cancer Institute,2 Program in Human Molecular Biology and Genetics, Departments of Oncological Sciences, Human Genetics, and Internal Medicine, University of Utah, Salt Lake City, Utah 84112

Received 3 September 1998/Returned for modification 22 October 1998/Accepted 10 December 1998

Hypertrophic growth of cardiac muscle cells is induced by a variety of physiological and pathological stimuli and is associated with a number of changes, including activation of genes such as atrial natriuretic factor. We found that two serum response element (SRE)-like DNA elements, one of which does not meet the consensus sequence and binds serum response factor (SRF) with low affinity, regulate the activity of this promoter. Surprisingly, the ability to induce the promoter by two different physiologic stimuli, as well as various activated transcription factors, including SRF-VP16, was primarily dependent upon the nonconsensus rather than the consensus SRE. This SRE controls the induction of gene expression via an unusual mechanism in that it is required to allow some, but not all, active transcription factors at unrelated sites on the promoter to stimulate gene expression. Thus, in addition to regulation of SRF activity by growth stimuli, regulation of a low-affinity SRE element controls inducible gene expression by modulating the ability of other transcription factors to stimulate the transcription machinery.

* Corresponding author. Mailing address: Huntsman Cancer Institute, Department of Oncological Sciences, 15 N 2030 E, Rm. 4160b, University of Utah, Salt Lake City, UT 84112. Phone: (801) 585 6332. Fax: (801) 585 3501. E-mail: andrew.thorburn{at}hci.utah.edu.

Molecular and Cellular Biology, March 1999, p. 1841-1852, Vol. 19, No. 3
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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