PLX283823

GSE106138: CBF- and Runx transcription factors promote adaptive NK cell responses [RNA-Seq]

• Organsim mouse
• Type RNASEQ
• Target gene
• Project ARCHS4

Natural killer (NK) cells are innate lymphocytes that possess features of adaptive immunity such as clonal expansion and generation of long-lived memory. Interleukin (IL)-12 signaling through its downstream transcription factor STAT4 is required for the generation of memory NK cells following expansion. Here, we identify gene loci that are highly enriched for STAT4 binding using ChIP-seq for STAT4 and the permissive histone mark H3K4me3 in activated NK cells. We found that promoter regions of Runx1 and Runx3 are targets of STAT4, and that STAT4 binding during NK cell activation induces epigenetic modifications of Runx gene loci resulting in increased expression. Furthermore, specific ablation of Runx1, Runx3, or their binding partner Cbfb in NK cells resulted in defective clonal expansion and memory formation during viral infection, with evidence for Runx1-mediated control of a cell cycle program. Thus, our study reveals a mechanism whereby STAT4-mediated epigenetic control of individual Runx transcription factors promotes the adaptive behavior of antiviral NK cells. SOURCE: Colleen Lau Memorial Sloan Kettering Cancer Center