Recently it has been elegantly demonstrated that genetic variants associated with differential binding of PU.1, a master transcription factor regulating myeloid development and having a substantial effect on neutrophils function (McKercher et al., 1996; Siwaponanan et al., 2017), are predominantly cell type specific, associated with specific chromatin state, and regulate enhancer-promoter interactions and downstream gene expression, exhibiting association with IBD susceptibility (Watt et al., 2021). The gene discussed is SPI1; the disease is inflammatory bowel disease.