GSE110862
Genome-wide binding profiles of JUNB in unstimulated HoxER-PU.1 WT and 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, neutrophil-intrinsic mechanisms adjusting an appropriate inflammatory response are unknown. Herein, 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, PU.1 acts as rheostat of the inflammatory chromatin state, safeguarding the neutrophil epigenome from undergoing uncontrolled activation prior to pathogenic stimulation. Overall design: Examination of JUNB occupany in unstimulated HoxER-PU.1 WT and PU.1 KO neutrophils by deep sequencing in duplicates.