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Regulation of IFN‐α/β genes: evidence for a dual function of the transcription factor complex ISGF3 in the production and action of IFN‐α/β
Author(s) -
Harada Hisashi,
Matsumoto Masahito,
Sato Mitsuharu,
Kashiwazaki Yasuo,
Kimura Tohru,
Kitagawa Motoo,
Yokochi Taeko,
SokPin Tan Rosemary,
Takasugi Tomohiro,
Kadokawa Yuzo,
Schindler Chris,
Schreiber Robert D.,
Noguchi Shigeru,
Taniguchi Tadatsugu
Publication year - 1996
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1046/j.1365-2443.1996.870287.x
Subject(s) - biology , transcription factor , promoter , stat1 , interferon , microbiology and biotechnology , gene , gene expression , signal transduction , virology , genetics
Background: Efficient production of interferons (IFNs) in virally infected cells is an essential aspect of the host defence. The transcription factor complex ISGF3 (IFN‐stimulated gene factor 3) was originally identified as a critical mediator of the IFN signal; it is formed upon IFN receptor (IFNR) stimulation and binds to ISREs (IFN‐stimulated response elements) to activate IFN‐inducible genes. It has recently been shown that the DNA binding component of ISGF3, p48 (ISGF3γ) also binds to virus‐inducible elements in the IFN‐α/β genes, suggesting a potential new role of p48 in IFN production. Results: Primary cells from mice with a targeted disruption of the p48 gene show severe defects in virus‐induced IFN ‐α/β gene expression. A similar defect was also observed in cells lacking type I IFNR or Stat1, further demonstrating the role of IFN signalling in the induction of these IFN genes. ISGF3 in fact binds to the virus‐inducible elements within the IFN ‐α/β promoters. We also provide evidence showing that these elements are additionally controlled by an unidentified factor(s) which presumably triggers the primary phase of IFN gene induction. Conclusions: Our results demonstrate that the IFN signal transducing complex ISGF3 plays a crucial role in IFN production and suggest that ISGF3 may participate directly in the activation of IFN ‐α/β promoters. This dual function of ISGF3 may insure the efficient operation of this cytokine system in the host defence.