SRA

Macrophages are plastic components of the immune system, critical to maintain tissue homeostasis. Their remarkable plasticity is achieved by rearranging their epigenome upon external signals. Here we show that during macrophage polarization, IL-4 activated STAT6 rearranges the accessibility of the genome and expands the RXR cistrome via chromatin binding and by the induction of a wave of transcription factors including PPAR?. PPAR? is indispensable in the establishment of RXR-bound de novo enhancers conferring enhanced receptor signaling. Unexpectedly, PPAR? and RXR are also needed to recruit P300 and RAD21 in an IL-4 dependent manner to STAT6 co-bound enhancers. In addition they function as bookmarking factors endowing the cell with an augmented STAT6 signaling upon restimulation. Collectively, these data imply that the expansion of the RXR cistrome is a key determinant of STAT6 mediated gene expression, by establishing and maintaining promoter-enhancer interactions and also functioning as transcriptional memory marks during macrophage polarization.