Genome-wide analysis of chromatin landscape in murine bone marrow derived eosinophils

We applied a global approach using broad-range, next-generation sequecing to identify a repertoire of eosinophil-specific enhancers. H3K4me1, H3K4me3, H3K27ac and PU.1 ChIPseq data was paired with ATAC and gene expression data from bmEos. Transcription factor motif analysis revealed enrichment for PU.1 in eosinophil enhancers, and ChIP-seq confirmed PU.1 binding in enhancer of genes highly expressed in eosinophils. Comparison of identified PU.1-bound enhancers with 3 publically available myeloid datasets (neutrophils, bone marrow derived macrophages and immature granulocytes) revealed 25% of PU.1-bound enhancers were unique to eosinophils - an eosinophil-specific PU.1 regulome. GO analysis of eosinophil-specific PU.1-bound enhancers revealed enrichmend for genes involved in migration, proliferation, degranulation and survival. Collectively, our data identify eosinophil-specific enhancers regulating key eosinophil genes through epigenetic mechanisms and TF binding. These findings are supportive of a dynamic, epigenetic eosinophil regulome underlying eosinophil function and diversity.