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. Author manuscript; available in PMC: 2020 Jun 1.
Published in final edited form as: Nat Immunol. 2019 Nov 19;20(12):1574–1583. doi: 10.1038/s41590-019-0466-2

Fig. 3 |. epigenomic regulation links type I IFN signaling to induction of inflammatory non-ISgs.

Fig. 3 |

Stimulation of macrophages with TNF leads to transient expression of TNF-target genes encoding inflammatory mediators, such as IL6 and TNF, followed by a state of tolerance in which signaling responses to TLR ligands are strongly suppressed, and chromatin is not activated (not depicted). In contrast to tolerization with TNF alone, co-stimulation with TNF plus IFN-α results in coordinate binding of IRFs and NF-κB, increased chromatin accessibility and increased positive histone marks, most notably H3K4me3 (top right). These genes are thereby bookmarked with primed chromatin and subsequently exhibit a robust transcriptional response even to very weak proximal TLR-induced signals, such as those in TNF-tolerized cells on TLR stimulation (bottom right). TSS, transcription start site; ac, acetyl; Pol, polymerase.