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Journal of Experimental Medicine, Vol 172, 661-664, Copyright © 1990 by Rockefeller University Press
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JC Chrivia, T Wedrychowicz, HA Young and KJ Hardy
Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas 77030.
An approach has been optimized permitting measurement of human cytokine reporter gene expression after transient transfection directly into purified human peripheral blood T lymphocytes. Comparing the expression of interleukin 2 (IL-2) CAT with a series of specially engineered gamma interferon (IFN-gamma) constructs, a fundamental difference in the molecular mechanisms regulating these two cytokines has been suggested. A potent, tissue-specific, constitutive-acting positive regulatory element was located between sequences -215 and -53 in the human IFN- gamma gene. Deletion analyses suggested that sequences slightly upstream, between positions -251 to -215, exerted a powerful dominant suppressive influence over that positive element. Negative elements appear to play a major role in controlling the regulation of human IFN- gamma gene expression. We thus propose a model of cytokine gene regulation in which selective derepression may be an important fundamental mechanism of induction and/or positive modulation.
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