Interferon stimulated binding of ISRE is cell type specific and is predicted by homeostatic chromatin state

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.