(Hypertension. 2001;38:332.)
© 2001 American Heart Association, Inc.
Scientific Contributions |
NF-Y Antagonizes Renin Enhancer Function by Blocking Stimulatory Transcription Factors
Departments of Internal Medicine and Physiology and Biophysics, University of Iowa, College of Medicine (Q.S., C.D.S.), Iowa City; and Department of Molecular and Cellular Biology, Roswell Park Cancer Institute (K.W.G.), Buffalo, NY.
Correspondence to Curt D. Sigmund, PhD, Chair, Molecular Biology Interdisciplinary Program, Director, Transgenic and Gene Targeting Facility, Department of Internal Medicine and Physiology & Biophysics, 2191 Medical Laboratory, University of Iowa, College of Medicine, Iowa City, IA 52242. E-mail curt-sigmund{at}uiowa.edu
Abstract—— We previously reported that the promoter proximal portion of the mouse renin enhancer contains a binding site for NF-Y (Ea) that overlaps with a positive regulatory element (Eb). In the context of the renin enhancer, NF-Y acts to oppose enhancer activity. We tested the hypothesis that NF-Y acts as a negative regulator by physically blocking the binding of transcription factors to element-b (Eb). Increasing the spacing between the NF-Y binding site (Ea) and Eb by 2, 5, or 10 nucleotides increased activity of the enhancer to the same extent as mutations abolishing NF-Y binding. The increase in transcription caused by increasing the spacing between Ea and Eb was not due to a shift of NF-Y from a negative regulator to a positive regulator because there was no loss of activity when Ea was also mutated. Oligonucleotides containing the normal or increased spacing mutants still allowed the binding of both NF-Y to Ea and transcription factors to Eb. In fact, we present evidence that both NF-Y and the Eb-binding factor(s) can each bind together on the same oligonucleotide containing either a 5- or 10-bp spacing between Ea and Eb. Our data strongly suggest that the mechanism by which NF-Y opposes renin enhancer activity is to sterically block the binding of factors to Eb.
Key Words: transcription • renin-angiotensin system • activator • repressor
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