The antiviral response induced by type I interferon (IFN) via the JAK-STAT signaling cascade activates hundreds of IFN-stimulated genes (ISGs) across human and mouse tissues but varies between cell types. However, the links between the underlying epigenetic features and the ISG profile are not well understood. We mapped ISGs, binding sites of the STAT1 and STAT2 transcription factors, chromatin accessibility, and histone H3 lysine modification by acetylation (ac) and mono-/tri-methylation (me1, me3) in mouse embryonic stem cells and fibroblasts before and after IFNβ treatment. A large fraction of ISGs and STAT-binding sites was cell type specific with promoter binding of a STAT1/2 complex being a key driver of ISGs. Furthermore, STAT1/2 binding to putative enhancers induced ISGs as inferred from a chromatin co-accessibility analysis. STAT1/2 binding was dependent on the chromatin context and positively correlated with preexisting H3K4me1 and H3K27ac marks in an open chromatin state, whereas 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.

中文翻译：

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表观遗传信号可指导小鼠细胞中细胞类型特异性干扰素β反应。

I 型干扰素 (IFN) 通过 JAK-STAT 信号级联诱导的抗病毒反应会激活人类和小鼠组织中数百个 IFN 刺激基因 (ISG)，但不同细胞类型之间存在差异。然而，潜在的表观遗传特征和 ISG 图谱之间的联系尚不清楚。我们绘制了 IFNβ 前后小鼠胚胎干细胞和成纤维细胞中的 ISG、STAT1 和 STAT2 转录因子的结合位点、染色质可及性以及组蛋白 H3 赖氨酸乙酰化 (ac) 和单/三甲基化 (me1、me3) 的图谱治疗。大部分 ISG 和 STAT 结合位点具有细胞类型特异性，STAT1/2 复合物的启动子结合是 ISG 的关键驱动因素。此外，根据染色质共可达性分析推断，STAT1/2 与推定增强子的结合诱导了 ISG。STAT1/2 结合依赖于染色质环境，并与开放染色质状态下预先存在的 H3K4me1 和 H3K27ac 标记呈正相关，而 H3K27me3 的存在具有抑制作用。因此，刺激前存在的染色质特征代表细胞类型特异性抗病毒反应的额外调节层。