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Nucleic Acids Research, 1992, Vol. 20, No. 7 1531-1538
© 1992


MOLECULAR BIOLOGY

Identification of novel factors that bind to the PRD I region of the human ß-interferon promoter

Simon T. Whiteside, Kanna V. Visvanathan{dagger} and Stephen Goodbourn*

Gene Expression Laboratory, Imperial Cancer Research Fund 44 Lincoln's Inn Fields, London WC2A 3PX, UK

*To whom correspondence should be addressed

Received January 21, 1992. Revised March 2, 1992. Accepted March 2, 1992.

Treatment of cells with virus or synthetic double-stranded RNA (dsRNA) leads to the transient transcriptional activation of the ß-interferon gene. Genetic analysis has revealed that the 5' regulatory sequence responsible for this induction contains multiple positive and negative elements. One of these, Positive Regulatory Domain I (PRD I), has been shown to bind the positively-acting transcription factor IRF-1. In this study we show that this element is inducible under conditions where IRF-1 cannot be detected, suggesting that additional cellular factors are involved in the Induction process. To investigate the existence of such factors we have analysed the range and properties of PRD l-binding activities present In HeLa cells. In addition to the repressor protein IRF-2, several novel factors can bind to PRD I in uninduced cells: two of these have properties consistent with a role in negative regulation; levels of two others increase upon priming, and may be alternative candidates for activators. Upon induction we also observe a novel factor whose appearance does not depend upon de novo protein synthesis, and which appears to be a truncated form of IRF-2. The potential involvement of these factors in regulating the ß-interferon gene is discussed.


{dagger}present address: Cold Spring Harbor Laboratories, Cold Spring Harbor, NY 11724, USA


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