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A single DNA response element can confer inducibility by both alpha- and gamma-interferons.
L E Reid1, A H Brasnett, C S Gilbert
1Imperial Cancer Research Fund Laboratories, Lincoln's Inn Fields, London, United Kingdom.
Summary
Researchers identified the 9-27 gene, which responds to interferons (IFNs). Its regulatory element, the IFN-stimulable response element (ISRE), is crucial for this response, suggesting context determines IFN specificity.
Area of Science:
- Molecular Biology
- Immunology
- Genetics
Background:
- The 1-8 gene family includes proteins inducible by interferons (IFNs).
- Interferons (IFNs) are critical signaling proteins in the immune system.
- Understanding gene regulation by IFNs is key to immune response mechanisms.
Purpose of the Study:
- To isolate and characterize the 9-27 gene, a member of the human 1-8 gene family.
- To investigate the role of the IFN-stimulable response element (ISRE) in mediating IFN-induced gene expression.
- To determine the specificity of ISREs in response to different types of IFNs.
Main Methods:
- Isolation and characterization of genomic and cDNA clones for the 9-27 gene.
- Analysis of the 5' flanking region, including identification of an ISRE.
- Functional analysis using constructs with native and mutated ISREs and a marker gene.
Main Results:
- A functional 9-27 gene encoding a 125-amino acid polypeptide was identified.
- The 9-27 gene's 5' flanking region contains an ISRE essential for response to both IFN-alpha and IFN-gamma.
- ISREs from 9-27 and 6-16 genes conferred dual IFN responsiveness to a marker gene, indicating context-dependent specificity.
Conclusions:
- The ISRE is a critical regulatory motif for IFN-inducible genes like 9-27.
- The specific sequence context surrounding an ISRE dictates its response to different types of interferons.
- This finding provides insight into the molecular mechanisms of interferon signaling and gene regulation.