Stem cells intrinsically express a subset of genes which are normally associated with interferon stimulation, and thus the innate immunity response. Expression of these interferon stimulated genes (ISG) in stem cells is independent of external stimuli such as viral infection. Here we show that the interferon regulatory factor 1, Irf1, is directly controlled by the murine formative pluripotency gene regulatory network and therefore upregulated in the transition from naive to formative pluripotency. IRF1 in turn binds to regulatory regions of a conserved set of ISGs and is required for their faithful expression in formative pluripotent cells. IRF1 also binds to an enhancer of the formative pluripotency transcription factor Oct6 and is partially required for upregulation of Oct6. IRF1 therefore acts as a link between the formative pluripotency network and the regulation of innate immunity genes in formative pluripotency.

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