A novel interferon-inducible domain: structural and functional analysis of the human interferon regulatory factor 1 gene promoter.
We have cloned and functionally characterized the human interferon regulatory factor 1 (IRF-1) gene promoter. The promoter contains a CpG island, with several GC boxes, a CAAT box, but no TATA box. IRF-1 mRNA is strongly induced by gamma interferon (IFN-gamma) but more weakly and transiently by IFN-alpha. There are several putative kappa B motifs and numerous AA(G/A)G(G/T)A and GAAANN motifs throughout the promoter. The IRF-1 promoter is not autoregulated by the IRF-1 gene product. IFN inducibility of the promoter was studied with 5' deletion mutants linked to a heterologous reporter gene. Gel mobility shift assays were used to show IFN-inducible factor binding to the IRF-1 promoter. These studies showed that IFN inducibility is conferred by a novel imperfect inverted-repeat arrangement of two GAAANN motifs within a domain, 130 nucleotides upstream of transcription initiation. This inverted repeat binds a factor upon induction with IFN and can confer IFN inducibility on a heterologous promoter. Conversely, point mutations of the inverted repeat are not IFN inducible when linked to the same heterologous promoter.
Sims
S H
SH
Department of Hematology, University of Texas M. D. Anderson Cancer Center, Houston 77030.
Cha
Y
Y
Romine
M F
MF
Gao
P Q
PQ
Gottlieb
K
K
Deisseroth
A B
AB
D001483:Base Sequence; D001665:Binding Sites; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation / Q000187:drug effects; D005796:Genes; D006801:Humans; D050856:Interferon Regulatory Factor-1; D007372:Interferons / Q000494:pharmacology*; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D010750:Phosphoproteins / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid; D014157:Transcription Factors / Q000378:metabolism*
D004268:DNA-Binding Proteins; C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; D016328:NF-kappa B; D009838:Oligodeoxyribonucleotides; D010750:Phosphoproteins; D012333:RNA, Messenger; D014157:Transcription Factors; D007372:Interferons