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PRC1 nanoglobules organize Hox chromatin during Drosophila embryogenesis.
Cell Discov, 12(1).
Polycomb group (PcG) proteins are required to maintain the silencing of keydevelopmental genes during development. In Drosophila, they bind to discretegenomic elements named Polycomb response elements (PREs). PcG proteins form twoclasses of complexes. Polycomb repressive complex 2 (PRC2) deposits H3K27me3, ahistone mark that covers large chromatin domains. The canonical PRC1 complex canbind to PREs as well as to the H3K27me3 mark. Inside the cell nucleus, whenanalyzed by confocal microscopy, the PcG subunits and associated chromatin arelocalized to polycomb foci. However, the lack of spatial resolution of thismethod impedes the precise localization of the polycomb machinery relative to itstarget chromatin. To resolve this long-standing problem, we analyzed Drosophilaembryos by superresolution stimulated emission depletion microscopy. We observedthat polycomb foci associated with Hox gene clusters are composed of multipledynamic PRC1 substructures, which we named "PRC1 nanoglobules". PREs are moreassociated with these nanoglobules than the surrounding H3K27me3 chromatin. Byimaging the entire Bithorax complex (BX-C) locus, we identified chromatinsubstructures that partially overlap with PRC1 nanoglobules, indicating that theyform different assemblies. Furthermore, polymer simulations suggest thatinteractions between PREs and PRC1 nanoglobules can drive the compaction andpositioning of the BX-C domain. Taken together, these data suggest that byestablishing the three-dimensional architecture of their target loci, PRC1nanoglobules are key molecular assemblies that maintain polycomb-dependentsilencing.
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