Expression profiling by high throughput sequencing Genome binding/occupancy profiling by high throughput sequencing
Summary
The antiviral response induced by type I interferon (IFN) via the JAK-STAT signaling cascade results in the activation of a set of IFN-stimulated genes (ISGs). This response varies between different cell types of the organism. However, the linkage between the underlying epigenetic features and innate immune response is not well understood. We mapped ISGs and STAT1 and STAT2 binding sites in mouse embryonic stem cells and differentiated cells before and after treatment with IFNβ together with histone acetylation (ac) and mono- and tri-methylation (me1, me3) marks at histone H3 lysine residues for H3K4me1, H3K4me3, H3K9ac, H3K27ac, H3K9me3 and H3K27me3. Many ISGs were cell type specific and displayed distinct STAT1/2 binding patterns at promoters. Furthermore, binding to putative enhancers at intergenic and intronic site was driving ISGs as inferred from a co-regulation analysis of open chromatin sites in single cells. Activator binding was dependent on the chromatin context and positively correlated with pre-existing H3K4me1 enrichment and open chromatin states while the presence of H3K27me3 had the opposite effect. Chromatin features present before stimulation direct the cell type specific response to type I IFNs. Thus, epigenetic signals represent an additional regulatory layer that is responsible for the tissue dependent activity of this signaling pathway. The mechanistic insight gained in our study could be exploited for modulating innate immune response during virus infection or cancer immunotherapy.
Overall design
RNA-seq, ChIP-seq, ATAC-seq, scRNA-seq and scATAC-seq of mouse embryonic stem cells compared to mouse embryonic fibroblasts and differentiated neuronal progenitor cells upon interferon beta treatment
Please note that processed data files generated from multiple samples are linked as Series supplementary files, along with 'readme.txt' describing the data.
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