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mSWI/SNF promotes Polycomb repression both directly and through genome-wide redistribution

Weber, Christopher M
Hafner, Antonina
Kirkland, Jacob G
Stanton, Benjamin Z
Boettiger, Alistair N
Crabtree, Gerald R
Published in Nature structural & molecular biology. 2021, vol. 28, no. 6, p. 501-511
Abstract The mammalian SWI/SNF complex, 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 mouse embryonic stem cells on short timescales. We report that rapid BAF depletion redistributes Polycomb repressive complexes PRC1 and PRC2 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 and 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.
Keywords AnimalsCRISPR-Cas SystemsCellsCulturedChromatin Assembly and Disassembly/genetics/physiologyDNA Helicases/genetics/metabolismDNA-Binding Proteins/physiologyEmbryonic Stem Cells/metabolismEpigenesisGeneticEpigenetic Repression/genetics/physiologyGene EditingGene Expression Regulation/genetics/physiologyGenesHomeoboxGenomeHEK293 CellsHomeodomain Proteins/genetics/metabolismHumansLoss of Function MutationMiceMultiprotein Complexes/physiologyNuclear Proteins/genetics/metabolismPolycomb-Group Proteins/physiologyProteolysisRecombinant Fusion Proteins/metabolismTranscription Factors/genetics/metabolism/physiology
PMID: 34117481
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Research group Régulation de la chromatine dans le développement du cerveau (1031)
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WEBER, Christopher M et al. mSWI/SNF promotes Polycomb repression both directly and through genome-wide redistribution. In: Nature Structural & Molecular Biology, 2021, vol. 28, n° 6, p. 501-511. doi: 10.1038/s41594-021-00604-7 https://archive-ouverte.unige.ch/unige:154515

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Deposited on : 2021-09-08

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