Model illustrating IRF8 function as an essential mediator within GATA2 genetic networks. Physiological levels of GATA2 establish a transcriptome (genes, black circles) with low Irf8 expression, which maintains a balance in myeloid and dendritic cell progenitors. Loss of the −77 enhancer and consequent reduction in GATA2 disrupts the network (gray circles), upregulating Irf8 and increasing proportions of MP, MDP, and CDP populations. Reducing Irf8, in the context of the −77 mutant allele, reversed granulocytic deficiencies and the excessive accumulation of dendritic cell progenitors.