A single DNA response element can confer inducibility by both alpha- and gamma-interferons.
Genomic and cDNA clones corresponding to 9-27, a member of the human 1-8 gene family highly inducible by alpha- and gamma-interferons (IFNs), have been isolated and characterized. A 1.7-kilobase genomic clone contains a complete functional gene with two exons, encoding a 125-amino acid polypeptide of unknown function. The 5' flanking region of the gene contains a 13-base-pair IFN-stimulable response element (ISRE), homologous to the ISREs of the 6-16, ISG 15, and ISG 54 genes, which are predominantly inducible by IFN-alpha, beta. Analysis of constructs containing native and mutated ISREs suggests that this motif is essential for the response of 9-27 to IFN-gamma as well as IFN-alpha. Furthermore, the 9-27 (GGAAATAGAAACT) and 6-16 (GGGAAAATGAAACT) ISREs can each confer a response to both types of IFN when placed on the 5' side of a marker gene. Since the 6-16 gene does not normally respond to IFN-gamma, the context of the ISRE must determine the specificity of the response.
Reid
L E
LE
Imperial Cancer Research Fund Laboratories, Lincoln's Inn Fields, London, United Kingdom.
Brasnett
A H
AH
Gilbert
C S
CS
Porter
A C
AC
Gewert
D R
DR
Stark
G R
GR
Kerr
I M
IM
D000595:Amino Acid Sequence; D001483:Base Sequence; D003360:Cosmids; D004247:DNA / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics; D004274:DNA, Recombinant / Q000302:isolation & purification; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000187:drug effects*; D009154:Mutation; D011994:Recombinant Proteins; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection
D004274:DNA, Recombinant; D007370:Interferon Type I; D011994:Recombinant Proteins; D007371:Interferon-gamma; D004247:DNA