Authors: | Paquette, R. L.; Ruby minosa, M.; Verma, M. C.; Nimer, S. D.; Phillip Koeffler, H. |
Article Title: | An interferon-γ activation sequence mediates the transcriptional regulation of the IgG Fc receptor type IC gene by interferon-γ |
Abstract: | Expression of the IgG Fc receptor type I (FcγRI) on myeloid cells is dramatically increased by treatment with interferon-γ (IFN-γ). We observed that FcγRI transcript levels in monoblast-like U937 cells were elevated within 3 hr and peaked 12 hr after exposure to IFN-γ. Treatment of U937 with IFN-γ for 9 hr in the presence of cycloheximide led to super-induction of FcγRI expression. Nuclear run-on analysis revealed that the rate of FcγRI transcription was increased by IFN-γ. Genomic sequence upstream of the FcγRIC gene was cloned and subjected to primer extension analysis, which demonstrated a single transcription initiation site without a TATA box. Transient transfections of CAT reporter gene constructs containing various FcγRIC promoter sequences into U937 cells revealed that a 20-bp region surrounding the transcription start site (-7 to +13) was capable of mediating transcription initiation and that an IFN-γ responsive element (GIRE) was present within 74 bp upstream of the transcription initiation site. A 17-bp sequence between positions -51 and -35 conferred IFN-γ responsiveness on a heterologous promoter. Double-stranded GIRE sequence, but not a scrambled sequence, was specifically bound by nuclear proteins from IFN-γ treated U937 cells. Gel shift experiments further showed that the STAT1α protein bound to the FcγRIC GIRE in response to IFN-γ treatment of U937 cells. The FcγRIC GIRE is homologous to the IFN-γ activation sequence (GAS) of the guanylate binding protein and to X box elements of class II MHC genes. Our results demonstrate that transcriptional regulation of the FcγRIC gene by IFN-γ involves the binding of STAT1α to a 17-bp GAS homology in the proximal promoter. © 1995. |
Keywords: | human cell; promoter region; dna-binding proteins; animal; mice; gene expression; cell line; genetic transcription; gene expression regulation; dna; molecular sequence data; gamma interferon; immunoglobulin g; base sequence; fc receptor; receptors, igg; dna sequence; binding sites; trans-activators; dna primers; monocyte; monocytes; sequence homology, nucleic acid; genes, mhc class ii; transcriptional regulation; stat protein; interferon type ii; promoter regions (genetics); trans-activation (genetics); interferon-γ; human; priority journal; article; support, non-u.s. gov't; support, u.s. gov't, p.h.s. |
Journal Title: | Molecular Immunology |
Volume: | 32 |
Issue: | 12 |
ISSN: | 0161-5890 |
Publisher: | Pergamon-Elsevier Science Ltd |
Date Published: | 1995-08-01 |
Start Page: | 841 |
End Page: | 851 |
Language: | English |
DOI: | 10.1016/0161-5890(95)00056-k |
PUBMED: | 7565811 |
PROVIDER: | scopus |
DOI/URL: | |
Notes: | Article -- Export Date: 28 August 2018 -- Source: Scopus |