show Abstracthide AbstractMacrophages are at the forefront of immune responses, and their transcriptional programs are modified by their tissue environment and in response to immunological challenge. Post-translational modifications of histones, such as histone H3 lysine 27 tri-methylation (H3K27me3) by the polycomb repressive complex 2 (PRC2), are tightly associated with epigenetic regulation of gene expression. To explore whether H3K27me3 is involved in either the establishment or function of the mononuclear phagocyte system, we selectively deleted the SUZ12 gene in one-week old mice, a core component of PRC2. SUZ12 ablation induced a rapid loss of the alveolar macrophage networks under both steady state and inflammatory conditions. Ablation of SUZ12 abrogated the proliferation of these cells required for their self-renewal. Overall design: TruSeq RNA libraries were generated from FACS purified alveolar macrophages from one week old wild type (4 biological replicates) or Suz12cKO (5 biological replicates) lung. Samples were sequenced with an Illumina NextSeq 500 sequencing system, producing between 19-56 million single-end 85 bp reads per sample.