C/EBPδ-induced epigenetic changes control the dynamic gene transcription of S100a8 and S100a9 .
| Autor: | Jauch-Speer SL; Institute of Immunology, University of Münster, Münster, Germany., Herrera-Rivero M; Department of Genetic Epidemiology, Institute of Human Genetics, University of Münster, Münster, Germany., Ludwig N; Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Münster, Münster, Germany., Véras De Carvalho BC; Institute of Immunology, University of Münster, Münster, Germany., Martens L; Institute of Immunology, University of Münster, Münster, Germany.; Department of Genetic Epidemiology, Institute of Human Genetics, University of Münster, Münster, Germany., Wolf J; Institute of Immunology, University of Münster, Münster, Germany., Imam Chasan A; Institute of Immunology, University of Münster, Münster, Germany., Witten A; Department of Genetic Epidemiology, Institute of Human Genetics, University of Münster, Münster, Germany.; Core Facility Genomics, Medical Faculty Münster, University of Münster, Münster, Germany., Markus B; Clinic for Cardiology, Angiology and Internal Intensive Medicine, University Hospital Marburg, Marburg, Germany., Schieffer B; Clinic for Cardiology, Angiology and Internal Intensive Medicine, University Hospital Marburg, Marburg, Germany., Vogl T; Institute of Immunology, University of Münster, Münster, Germany., Rossaint J; Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Münster, Münster, Germany., Stoll M; Department of Genetic Epidemiology, Institute of Human Genetics, University of Münster, Münster, Germany.; CARIM Cardiovascular Research School, Department of Biochemistry, Genetic Epidemiology and Statistical Genetics, Maastricht University, Maastricht, Netherlands., Roth J; Institute of Immunology, University of Münster, Münster, Germany., Fehler O; Institute of Immunology, University of Münster, Münster, Germany. |
|---|---|
| Jazyk: | angličtina |
| Zdroj: | ELife [Elife] 2022 May 11; Vol. 11. Date of Electronic Publication: 2022 May 11. |
| DOI: | 10.7554/eLife.75594 |
| Abstrakt: | The proinflammatory alarmins S100A8 and S100A9 are among the most abundant proteins in neutrophils and monocytes but are completely silenced after differentiation to macrophages. The molecular mechanisms of the extraordinarily dynamic transcriptional regulation of S100a8 and S100a9 genes, however, are only barely understood. Using an unbiased genome-wide CRISPR/Cas9 knockout (KO)-based screening approach in immortalized murine monocytes, we identified the transcription factor C/EBPδ as a central regulator of S100a8 and S100a9 expression. We showed that S100A8/A9 expression and thereby neutrophil recruitment and cytokine release were decreased in C/EBPδ KO mice in a mouse model of acute lung inflammation. S100a8 and S100a9 expression was further controlled by the C/EBPδ antagonists ATF3 and FBXW7. We confirmed the clinical relevance of this regulatory network in subpopulations of human monocytes in a clinical cohort of cardiovascular patients. Moreover, we identified specific C/EBPδ-binding sites within S100a8 and S100a9 promoter regions, and demonstrated that C/EBPδ-dependent JMJD3-mediated demethylation of H3K27me Competing Interests: SJ, MH, NL, BV, LM, JW, AI, AW, BM, BS, TV, JR, MS, JR, OF No competing interests declared (© 2022, Jauch-Speer et al.) |
| Databáze: | MEDLINE |
| Externí odkaz: |
|