Interferons reshape the 3D conformation and accessibility of macrophage chromatin
| Autor: | Thomas Decker, Andreas Sommer, Stephan Grüner, Ekaterini Platanitis, Alexander Vogt, Laura Boccuni, Aarathy Ravi Sundar Jose Geetha, Maria Novachkova, Mathias Müller |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Cell biology
Multidisciplinary Innate immune system Molecular biology Science Inducible Gene-Expression Transcriptional Activation Topological Domains Ifn-Gamma Cohesin Stat Promoter Element Organization Enhancers Epigenome Biology Chromatin Histone Transcriptional regulation biology.protein Molecular mechanism of gene regulation Nucleosome Epigenetics Signal transduction Epigenomics |
| Zdroj: | iScience, Vol 25, Iss 3, Pp 103840-(2022) |
| ISSN: | 2589-0042 |
| Popis: | Summary: Engagement of macrophages in innate immune responses is directed by type I and type II interferons (IFN-I and IFN-γ, respectively). IFN triggers drastic changes in cellular transcriptomes, executed by JAK-STAT signal transduction and the transcriptional control of interferon-stimulated genes (ISG) by STAT transcription factors. Here, we study the immediate-early nuclear response to IFN-I and IFN-γ in murine macrophages. We show that the mechanism of gene control by both cytokines includes a rapid increase of DNA accessibility and rearrangement of the 3D chromatin contacts particularly between open chromatin of ISG loci. IFN-stimulated gene factor 3 (ISGF3), the major transcriptional regulator of ISG, controlled homeostatic and, most notably, induced-state DNA accessibility at a subset of ISG. Increases in DNA accessibility correlated with the appearance of activating histone marks at surrounding nucleosomes. Collectively our data emphasize changes in the three-dimensional nuclear space and epigenome as an important facet of transcriptional control by the IFN-induced JAK-STAT pathway. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|