Nucleic Acids Research, 1994, Vol. 22, No. 6 1108-1114
© 1994
MOLECULAR BIOLOGY |
Identification and characterization of a novel repressor site in the human tumor necrosis factor 
gene
Department of Microbial Chemotherapeutics and Molecular Genetics, Merck Research Laboratories PO Box 2000, Rahway, NJ 07065, USA
* To whom correspondence should be addressed
Received June 11, 1993. Revised February 17, 1994. Accepted February 17, 1994.
In human monocytic cell lines, tumor necrosis factor 
(TNF) expression is induced by phorbol myrlstate acetate (PMA). We have identified positive and negative cls-acting elements in the TNF promoter by deletion analysis. Here we present the initial characterization of the repressor element. The repressor element was shown to function in either orientation and at various distances upstream from the positive element of the TNF promoter. The TNF repressor site (TRS) has been localized to a 25 bp region between base pairs –254 and –230 in the promoter. This region contains a 10 bp sequence with homology to the binding site of the activator protein AP-2. Mutation of the 6 C's of this 10 bp AP-2-llke site abolish TRS repressor function. However, this AP-2-llke site is not a binding site for AP-2 protein based on gel retardation analysis. In addition, a well-characterized AP-2 binding site placed upstream of the positive element of the TNF gene did not cause repression. Therefore, this repression is very likely mediated by a novel protein(s) which interacts with the AP-2 consensus site in the TRS.
+Present address: Baxter Diagnostics. Miami. FL 33174, USA
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