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Correspondence to:
Peter A. Edwards.
The current studies define the role of three distinct cis-elements in the proximal promoter of the rat farnesyl diphosphate (FPP) synthase gene. The three cis-elements, a sterol regulatory element 3 (SRE-3) flanked by an ATTGG motif (inverted CCAAT box), and a CCAAT box, form a sterol regulatory unit that is necessary and sufficient for sterol-regulated expression of FPP synthase promoter-reporter genes. FPP synthase promoter-reporter genes, that contain promoters with either wild-type nucleotide sequences or mutations in one or more of the three cis-elements, were transiently transfected into CV-1 cells. The activity of the wild-type promoter-reporter gene increased when the cells were incubated in sterol-depleted media or when the cells were co-transfected with a plasmid encoding the mature form of SRE binding protein (SREBP-1a).
The results with the mutant promoter-reporter genes demonstrated that all three cis-elements were necessary for normal expression/regulation of the reporter gene by either sterols or by co-expressed SREBP-1a. Gel mobility shift assays demonstrated that the synergistic binding of SREBP-1a to SRE-3 was dependent on the binding of recombinant nuclear factor Y (NF-Y) to the DNA, consistent with the in vivo regulation studies.—Jackson, S. M., J. Ericsson, R. Mantovani, and P. A. Edwards. Synergistic activation of transcription by nuclear factor Y and sterol regulatory element binding protein. J. Lipid Res. 1998. 39: 767–776.
Supplementary key words:
SREBP-1a, SRE-3
Copyright © 1998 by Lipid Research, Inc.
Original Article
Synergistic activation of transcription by nuclear factor Y and sterol regulatory element binding protein
Simon M. Jacksona,
Johan Ericssona,
Roberto Mantovanic, and
Peter A. Edwardsa,b
a Departments of Biological Chemistry and Medicine Molecular Biology Institute, Los Angeles, CA 90095
b Departments of Biological Chemistry and Medicine University of California-Los Angeles, Los Angeles, CA 90095
c Departimento di Genetica e Biologia dei Microorganismi, Universita di Milano, 20133 Milano, Italy
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