Epigenetic signals that direct cell type specific interferon beta response in mouse cells
Abstract The antiviral response induced by type I interferon (IFN) via the JAK-STAT signaling cascade activates hundreds of IFN-stimulated genes (ISGs). While this response occurs essentially in all human and mouse tissues it varies between different cell types. However, the linkage between the underlying epigenetic features and the ISG pattern of a given cell is not well understood. We mapped ISGs, binding sites of the STAT1 and STAT2 transcription factors and chromatin features in three different mouse cell types (embryonic stem cells, neural progenitor cells and embryonic fibroblasts) before and after treatment with IFNβ. The analysis included gene expression, chromatin accessibility and histone H3 lysine modification by acetylation (ac) and mono-/tri-methylation (me1, me3). A large fraction of ISGs and STAT binding sites were cell type specific with promoter binding of a STAT1-STAT2 complex (STAT1/2) being a key driver of ISG induction. Furthermore, STAT1/2 binding to putative enhancers at intergenic and intronic sites induced ISG expression as inferred from a chromatin co-accessibility analysis. STAT1/2 binding was dependent on the chromatin context and positively correlated with pre-existing H3K4me1 and H3K27ac marks in an open chromatin state while the presence of H3K27me3 had an inhibitory effect. Thus, chromatin features present before stimulation represent an additional regulatory layer for the cell type specific antiviral response..
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Preprint| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
bioRxiv.org - (2024) vom: 29. Apr. Zur Gesamtaufnahme - year:2024 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Muckenhuber, Markus [VerfasserIn] |
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| doi: |
10.1101/2022.02.26.481127 |
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| PPN (Katalog-ID): |
XBI035350881 |
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| 520 | |a Abstract The antiviral response induced by type I interferon (IFN) via the JAK-STAT signaling cascade activates hundreds of IFN-stimulated genes (ISGs). While this response occurs essentially in all human and mouse tissues it varies between different cell types. However, the linkage between the underlying epigenetic features and the ISG pattern of a given cell is not well understood. We mapped ISGs, binding sites of the STAT1 and STAT2 transcription factors and chromatin features in three different mouse cell types (embryonic stem cells, neural progenitor cells and embryonic fibroblasts) before and after treatment with IFNβ. The analysis included gene expression, chromatin accessibility and histone H3 lysine modification by acetylation (ac) and mono-/tri-methylation (me1, me3). A large fraction of ISGs and STAT binding sites were cell type specific with promoter binding of a STAT1-STAT2 complex (STAT1/2) being a key driver of ISG induction. Furthermore, STAT1/2 binding to putative enhancers at intergenic and intronic sites induced ISG expression as inferred from a chromatin co-accessibility analysis. STAT1/2 binding was dependent on the chromatin context and positively correlated with pre-existing H3K4me1 and H3K27ac marks in an open chromatin state while the presence of H3K27me3 had an inhibitory effect. Thus, chromatin features present before stimulation represent an additional regulatory layer for the cell type specific antiviral response. | ||
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| 700 | 1 | |a Lander, Isabelle |e verfasserin |0 (orcid)0000-0001-9811-3836 |4 aut | |
| 700 | 1 | |a Müller-Ott, Katharina |e verfasserin |4 aut | |
| 700 | 1 | |a Mallm, Jan-Philipp |e verfasserin |0 (orcid)0000-0002-7059-4030 |4 aut | |
| 700 | 1 | |a Klett, Lara C. |e verfasserin |0 (orcid)0000-0003-2565-5268 |4 aut | |
| 700 | 1 | |a Knotz, Caroline |e verfasserin |4 aut | |
| 700 | 1 | |a Hechler, Jana |e verfasserin |4 aut | |
| 700 | 1 | |a Kepper, Nick |e verfasserin |4 aut | |
| 700 | 1 | |a Erdel, Fabian |e verfasserin |0 (orcid)0000-0003-2888-7777 |4 aut | |
| 700 | 1 | |a Rippe, Karsten |e verfasserin |0 (orcid)0000-0001-9951-9395 |4 aut | |
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