Loss of Usp22 enhances histone H2B monoubiquitination and stimulates intracellular and systemic interferon immunity
| Autor: | Hans-Reimer Rodewald, Thomas Winkler, Rodriguez Correa E, Xi Wang, Robyn Laura Kosinsky, Dietlein N, Erbil B, Daniel B. Lipka, Yvonne Begus-Nahrmann, Steven A. Johnsen |
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| Rok vydání: | 2021 |
| Předmět: |
0303 health sciences
Innate immune system biology Virus 3. Good health Cell biology 03 medical and health sciences 0302 clinical medicine Histone Immune system Interferon Immunity 030220 oncology & carcinogenesis biology.protein Histone H2B medicine Monoubiquitination 030304 developmental biology medicine.drug |
| Popis: | Interferons protect from virus infections by inducing hundreds of interferon-stimulated genes (ISG) which orchestrate anti-viral adaptive and innate immunity. Upon viral infection or type I interferon (IFN) stimulation of cell lines, a histone modification, monoubiquitinated histone 2B (H2Bub1), increases at ISG loci, raising the possibility that a specific chromatin state can broadly stimulate IFN immunity in vivo. Here we show that, in the absence of virus infection or elevated interferon levels, mice lacking the relevant deubiquitinase, Usp22, in immune cells have elevated H2Bub1 levels. Hypermonoubiquitinated H2B is physically associated with dozens of ISG loci, and expression of large numbers of ISG is upregulated. This epigenetic state promotes intracellular and systemic immune phenotypes akin to adaptive and innate interferon immunity, and thereby identifies Usp22 as a negative regulator of interferon immunity. |
| Databáze: | OpenAIRE |
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