GSE110864
Transcritpional profiling of unstimulated and Candida albicans stimulated HoxER-PU.1 WT and HoxER-PU.1 KO neutrophils
Neutrophils are essential first line defense cells against invading pathogens, yet their inappropriate activation contributes to immunological diseases and can cause collateral tissue damage. However, if and how neutrophils cell-intrinsically titrate their inflammatory response remains unknown. Here, we conditionally deleted PU.1, a key myeloid transcription factor, from the neutrophils of mice undergoing fungal infection, and then performed comprehensive epigenomic profiling. We find that a major function of PU.1 is to restrain the neutrophils' immune response by broadly suppressing genomic enhancer outputs via recruiting histone deacetylase activity, thereby limiting the immune-stimulatory AP1-transcription factor JUNB from entering chromatin. Thus, neutrophils rely on a direct PU.1 repressor function as rheostat of the inflammatory chromatin state, safeguarding their epigenome from undergoing uncontrolled activation prior to pathogenic stimulation. Overall design: mRNA profiles of unstimulated and C. albicans stimulated wildtype and PU.1 deleted neutrophils were generated by deep sequencing in duplicates or triplicates.