Interferon-induced nuclear factors that bind a shared promoter element correlate with positive and negative transcriptional control.
Human alpha- and beta-interferons (IFNs) stimulate rapid but transient increases in transcription from a set of previously quiescent genes. Protein synthesis is not required for initial stimulation, but duration of the response is limited to a few hours by a process requiring synthesis of new proteins. An IFN-stimulated response element (ISRE) was identified 5' to an inducible gene by deletion analysis and point mutagenesis, and sequence comparisons with other promoters defined the consensus element YAGTTTC(A/T)YTTTYCC. Two classes of IFN-inducible nuclear factors were found that bind to the ISRE. The most rapidly induced factor appeared without new protein synthesis, whereas a second factor required active protein synthesis for its appearance and maintenance. The kinetics of appearance and loss of these binding activities correlate with the activation and repression of IFN-stimulated genes. These different IFN-activated or induced factors may bind sequentially to the same essential promoter element to first increase and then repress transcription.
Levy
D E
DE
Laboratory of Molecular Cell Biology, Rockefeller University, New York, New York 10021.
Kessler
D S
DS
Pine
R
R
Reich
N
N
Darnell
J E
JE
D001483:Base Sequence; D004247:DNA; D004268:DNA-Binding Proteins / Q000502:physiology; D003851:Deoxyribonucleases; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D007370:Interferon Type I / Q000502:physiology*; D008957:Models, Genetic; D009154:Mutation; D011401:Promoter Regions, Genetic; D012045:Regulatory Sequences, Nucleic Acid; D014157:Transcription Factors / Q000302:isolation & purification* / Q000502:physiology; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D007370:Interferon Type I; D014157:Transcription Factors; D004247:DNA; D003851:Deoxyribonucleases