期刊
FRONTIERS IN IMMUNOLOGY
卷 12, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2021.651254
关键词
interferon; JAK-STAT signaling pathway; signal transduction; gene regulation; ISGF3; GAF
类别
资金
- NIH [R01AI132835]
- UCLA Bruins in Genomics Undergraduate Research Program
- Ruth L. Kirschstein National Research Service Award [AI007323]
- Chancellor's Postdoctoral Fellowship at UCLA
- Irving and Jean Stone Foundation
- Oppenheimer Award of the UCLA Undergraduate Research Fellows Program
- UCLA Department of Medicine Specialty Training and Advanced Research Program
IFN-beta signaling can activate both ISGF3 and GAF in murine lung epithelial cells, with GAF potentially acting as a dose-sensitive amplifier of ISG expression to enhance antiviral immunity.
Interferon beta (IFN-beta) signaling activates the transcription factor complex ISGF3 to induce gene expression programs critical for antiviral defense and host immune responses. It has also been observed that IFN-beta activates a second transcription factor complex, gamma-activated factor (GAF), but the significance of this coordinated activation is unclear. We report that in murine lung epithelial cells (MLE12) high doses of IFN-beta indeed activate both ISGF3 and GAF, which bind to distinct genomic locations defined by their respective DNA sequence motifs. In contrast, low doses of IFN-beta preferentially activate ISGF3 but not GAF. Surprisingly, in MLE12 cells GAF binding does not induce nearby gene expression even when strongly bound to the promoter. Yet expression of interferon stimulated genes is enhanced when GAF and ISGF3 are both active compared to ISGF3 alone. We propose that GAF may function as a dose-sensitive amplifier of ISG expression to enhance antiviral immunity and establish pro-inflammatory states.
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