RNA-seq profiling of bone marrow-derived alveolar macrophages from wildtype and Suz12 knockout mice

Macrophages 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 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: C57BL/6-Ly5.1 mice were lethally irradiated and reconstituted with either a ratio of 90% wt Ly5.2: 10% wt Ly5.1, or 90% Suz12 cKO Ly5.2: 10% wt ly5.1. TruSeq RNA libraries were generated from alveolar macrophages selected by flow cytometry from wild type mice (4 biological replicates) or Suz12cKO (3 biological replicates) lung. Samples were sequenced with an Illumina NextSeq 500 sequencing system, producing between 14-20 million single-end 85 bp reads per sample.