Acetylation of C/EBPε is essential for terminal neutrophil differentiation and function. C/EBPε is acetylated during granulocytic differentiation toward neutrophils by lysine acetylases (KAC, eg, p300) or lysine deacetylase inhibitors (KDACi, eg, nicotinamide inhibiting KDAC SIRT1). Acetylation on K121 and K198 is essential for terminal differentiation of neutrophils and expression of secondary granule proteins. Differential acetylation of C/EBPε could be important for determining differentiation along the neutrophil or eosinophil lineages.