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Learn MoreInterleukin-4 (IL-4) activates macrophages to adopt a distinct phenotype important for tissue repair and helminth infection, but the molecular basis of chromatin remodeling in response to IL-4 stimulation is not understood. We find that IL-4 activation of terminally differentiated macrophages in mice is accompanied by cell-type-specific chromatin remodeling in regions enriched with binding motifs of the pioneer transcription factor PU.1. Mutation studies based on natural genetic variation between C57BL/6 and BALB/c mouse strains demonstrate that accessibility of these IL-4 induced regions can be regulated through differences in DNA shape, without disruption of pioneer factor motifs. We propose a model whereby DNA shape features of stimulation-dependent genomic elements contribute to differences in the accessible chromatin landscape of alternatively activated macrophages on different genetic backgrounds. SOURCE: Mei San Tang Washington University in St Louis
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