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标题：Interferons reshape the 3D conformation and accessibility of macrophage chromatin
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作者：Ekaterini Platanitis ; Stephan Gruener ; Aarathy Ravi Sundar Jose Geetha 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2022
卷号：25
期号：3
页码：1-27
DOI：10.1016/j.isci.2022.103840
语种：English
出版社：Elsevier
摘要：SummaryEngagement 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.Graphical abstractDisplay OmittedHighlights•Type I IFN and IFN-γ rapidly increase chromatin accessibility at many target loci•Both IFN types cause rapid chromatin loop rearrangements at target loci•Loop formation increases between regions of accessible promoter chromatin•Large contribution of transcription factor ISGF3 to gene control by both IFN typesMolecular biology; Molecular mechanism of gene regulation; Epigenetics; Cell biology