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<p>Polycomb group (PcG) proteins are required to maintain the silencing of key developmental genes during development. In <i>Drosophil</i>a, they bind to discrete genomic elements named Polycomb response elements (PREs). PcG proteins form two classes of complexes. Polycomb repressive complex 2 (PRC2) deposits H3K27me3, a histone mark that covers large chromatin domains. The canonical PRC1 complex can bind to PREs as well as to the H3K27me3 mark. Inside the cell nucleus, when analyzed by confocal microscopy, the PcG subunits and associated chromatin are localized to polycomb foci. However, the lack of spatial resolution of this method impedes the precise localization of the polycomb machinery relative to its target chromatin. To resolve this long-standing problem, we analyzed <i>Drosophila</i> embryos by superresolution stimulated emission depletion microscopy. We observed that polycomb foci associated with <i>Hox</i> gene clusters are composed of multiple dynamic PRC1 substructures, which we named “PRC1 nanoglobules”. PREs are more associated with these nanoglobules than the surrounding H3K27me3 chromatin. By imaging the entire Bithorax complex (BX-C) locus, we identified chromatin substructures that partially overlap with PRC1 nanoglobules, indicating that they form different assemblies. Furthermore, polymer simulations suggest that interactions between PREs and PRC1 nanoglobules can drive the compaction and positioning of the BX-C domain. Taken together, these data suggest that by establishing the three-dimensional architecture of their target loci, PRC1 nanoglobules are key molecular assemblies that maintain polycomb-dependent silencing.</p>

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PRC1 nanoglobules organize Hox chromatin during Drosophila embryogenesis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月7日

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  • Thierry Cheutin,
  • Nazli Akilli,
  • Marco Di Stefano,
  • Paul-Swann Puel,
  • Lauriane Fritsch,
  • Daniel Jost,
  • Giacomo Cavalli

摘要

Polycomb group (PcG) proteins are required to maintain the silencing of key developmental genes during development. In Drosophila, they bind to discrete genomic elements named Polycomb response elements (PREs). PcG proteins form two classes of complexes. Polycomb repressive complex 2 (PRC2) deposits H3K27me3, a histone mark that covers large chromatin domains. The canonical PRC1 complex can bind to PREs as well as to the H3K27me3 mark. Inside the cell nucleus, when analyzed by confocal microscopy, the PcG subunits and associated chromatin are localized to polycomb foci. However, the lack of spatial resolution of this method impedes the precise localization of the polycomb machinery relative to its target chromatin. To resolve this long-standing problem, we analyzed Drosophila embryos by superresolution stimulated emission depletion microscopy. We observed that polycomb foci associated with Hox gene clusters are composed of multiple dynamic PRC1 substructures, which we named “PRC1 nanoglobules”. PREs are more associated with these nanoglobules than the surrounding H3K27me3 chromatin. By imaging the entire Bithorax complex (BX-C) locus, we identified chromatin substructures that partially overlap with PRC1 nanoglobules, indicating that they form different assemblies. Furthermore, polymer simulations suggest that interactions between PREs and PRC1 nanoglobules can drive the compaction and positioning of the BX-C domain. Taken together, these data suggest that by establishing the three-dimensional architecture of their target loci, PRC1 nanoglobules are key molecular assemblies that maintain polycomb-dependent silencing.