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Updated: May 31, 2026
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A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF3
Published on: January 24, 2016
E3 ligase UHRF2 hijacks nuclear TBK1 to epigenetically repress type I interferons expression
Wenwen Huang1,2, Renjie Song3, Qicong Shen2
1Institute of Immunology, Zhejiang University School of Medicine, Hangzhou 310058, China.
International Journal of Biological Sciences
|May 29, 2026
Summary
The E3 ubiquitin ligase UHRF2 epigenetically silences type I interferon (IFN-I) genes. UHRF2 deficiency in mice enhances antiviral immunity by overproducing IFN-I, suggesting therapeutic potential.
Area of Science:
- Immunology
- Epigenetics
- Molecular Biology
Background:
- Type I interferons (IFN-I) are crucial for host defense against viruses but their dysregulation causes autoimmune diseases.
- Understanding the precise regulation of IFN-I is critical for managing immune-related disorders.
Purpose of the Study:
- To elucidate the epigenetic mechanisms controlling type I interferon (IFN-I) gene transcription.
- To identify novel regulators involved in immune homeostasis and antiviral responses.
Main Methods:
- Investigated the role of E3 ubiquitin ligase UHRF2 in IFN-I regulation.
- Utilized viral infection models and UHRF2-deficient mice.
- Examined protein-protein interactions (UHRF2-HDAC1) and epigenetic modifications (histone lactylation).
Main Results:
- UHRF2 acts as an epigenetic repressor of IFN-I genes by stabilizing HDAC1.
- The UHRF2-HDAC1 complex removes histone H4K12 lactylation, silencing IFN-I transcription.
- UHRF2-deficient mice show enhanced resistance to viral infections due to IFN-I overproduction.
Conclusions:
- A novel mechanism involving nuclear TBK1, UHRF2, and HDAC1 regulates immune homeostasis via histone delactylation.
- UHRF2 is a key epigenetic regulator of IFN-I, offering a potential therapeutic target for viral infections and autoimmune diseases.
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