Characterization of transcriptional and epigenetic changes during mouse alternative macrophage activation

The molecular basis of signal-dependent transcriptional activation has been extensively studied in macrophage polarization, however our understanding remains limited regarding the molecular determinants of repression. Here we showed that IL-4 activated STAT6 transcription factor is required for the direct transcriptional repression of a large number of genes during mouse alternative macrophage polarization. Repression results in decreased lineage-determining transcription factor, p300 coactivator and RNA polymerase II binding followed by reduced enhancer RNA expression, H3K27 acetylation and chromatin accessibility. In addition, STAT6-repressed enhancers showed extensive overlap with the NF-?B p65 transcription factor cistrome and exhibited decreased responsiveness to lipopolysaccharide after IL-4 stimulus on a subset of genes.