mSWI/SNF promotes polycomb repression both directly and through genome-wide redistribution [ChIP-seq]

The mammalian SWI/SNF, or BAF complex, has a conserved and direct role in antagonizing polycomb-mediated repression. Yet, BAF also promotes repression by polycomb in stem cells and cancer. How BAF both antagonizes and promotes polycomb-mediated repression remains unknown. Here, we utilize targeted protein degradation to dissect the BAF-polycomb axis in embryonic stem cells on short timescales. We report that rapid BAF depletion redistributes PRC1 and PRC2 complexes from highly occupied domains, like Hox clusters, to weakly occupied sites normally opposed by BAF. Polycomb redistribution from highly repressed domains results in their decompaction, gain of active epigenomic features, and transcriptional derepression. Surprisingly, through dose-dependent degradation of PRC1 & PRC2 we identify a conventional role for BAF in polycomb-mediated repression, in addition to global polycomb redistribution. These findings provide new mechanistic insight into the highly dynamic state of the Polycomb-Trithorax axis. Overall design: We conducted ChIPseq with mES cell lines where Smarca4 (Brg1) can be targeted for degradation with auxin or Ring1A-/-;Ring1Bfl/fl; Rosa26::CreERT2 ES cells . Ring1b and Suz12 binding were assayed in quadruplicate. Histone marks and BAF155 were analyzed in duplicate.