A low-affinity serum response element allows other transcription factors to activate inducible gene expression in cardiac myocytes

Hypertrophic growth of cardiac muscle cells is induced by a variety of phys iological and pathological stimuli and is associated with a number of chang es, including activation of genes such as atrial natriuretic factor. We fou nd that two serum response element (SRE)-like DNA elements, one of which do es not meet the consensus sequence and binds serum response factor (SRF) wi th low affinity, regulate the activity of this promoter. Surprisingly, the ability to induce the promoter by two different physiologic stimuli, as wel l as various activated transcription factors, including SRF-VP16, was prima rily dependent upon the nonconsensus rather than the consensus SRE. This SR E controls the induction of gene expression via an unusual mechanism in tha t it is required to allow some, but not all, active transcription factors a t unrelated sites on the promoter to stimulate gene expression. Thus, in ad dition 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 machi nery.