Leviyang Sivan
Department of Mathematics and Statistics, Georgetown University, District of Columbia 20057, USA.
Cytokine X. 2021 Jul 17;3(4):100056. doi: 10.1016/j.cytox.2021.100056. eCollection 2021 Dec.
The type I interferon (IFN) signaling pathway involves binding of the transcription factor ISGF3 to IFN-stimulated response elements, ISREs. Gene expression under IFN stimulation is known to vary across cell types, but variation in ISGF3 binding to ISRE across cell types has not been characterized. We examined ISRE binding patterns under IFN stimulation across six cell types using existing ChIPseq datasets. We find that ISRE binding is largely cell specific for ISREs distal to transcription start sites (TSS) and largely conserved across cell types for ISREs proximal to TSS. We show that bound ISRE distal to TSS associate with differential expression of ISGs, although at weaker levels than bound ISRE proximal to TSS. Using existing ATACseq and ChIPseq datasets, we show that the chromatin state of ISRE at homeostasis is cell type specific and is predictive of cell specific, ISRE binding under IFN stimulation. Our results support a model in which the chromatin state of ISRE in enhancer elements is modulated in a cell type specific manner at homeostasis, leading to cell type specific differences in ISRE binding patterns under IFN stimulation.
I型干扰素（IFN）信号通路涉及转录因子ISGF3与IFN刺激反应元件（ISRE）的结合。已知IFN刺激下的基因表达在不同细胞类型中存在差异，但不同细胞类型中ISGF3与ISRE的结合差异尚未得到表征。我们使用现有的ChIPseq数据集检查了六种细胞类型在IFN刺激下的ISRE结合模式。我们发现，对于转录起始位点（TSS）远端的ISRE，ISRE结合在很大程度上具有细胞特异性，而对于TSS近端的ISRE，ISRE结合在不同细胞类型之间基本保守。我们表明，TSS远端的结合ISRE与ISG的差异表达相关，尽管其水平低于TSS近端的结合ISRE。利用现有的ATACseq和ChIPseq数据集，我们表明稳态下ISRE的染色质状态具有细胞类型特异性，并且可以预测IFN刺激下细胞特异性的ISRE结合。我们的结果支持一种模型，即增强子元件中ISRE的染色质状态在稳态下以细胞类型特异性方式受到调节，导致IFN刺激下ISRE结合模式的细胞类型特异性差异。
