A Polycomb domain found in committed cells impairs differentiation when introduced into PRC1 in pluripotent cells

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BAP1 enhances Polycomb repression by counteracting widespread H2AK119ub1 deposition and chromatin condensation

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PRC2.1- and PRC2.2-specific accessory proteins drive recruitment of different forms of canonical PRC1

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The time of timing: how Polycomb proteins regulate neurogenesis

The study of mammalian corticogenesis has revealed a critical role for Polycomb group (PcG) factors in timing the execution of developmental choices. Meanwhile, the study of post-translational modifications of PcG factors marks a symmetrical point, namely that the activity of PcG proteins is itself timed in a manner that links progression through the cell cycle to targeting of downstream genes. Finally, in a third symmetrical twist, the studies that dissect the timing of neural fate by Polycomb are also uncovering the importance of timing in the experimental mutation, since ablation of the same PcG member at different developmental stages yields dramatically different results. Here, I weave together these three lines of evidence and develop a unifying model that clarifies the dynamics of Polycomb function in neural development and defines the salient challenges ahead.     

Unique Structural Platforms of Suz12 Dictate Distinct Classes of PRC2 for Chromatin Binding

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The BAF and PRC2 Complex Subunits Dpf2 and Eed Antagonistically Converge on Tbx3 to Control ESC Differentiation

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Distinct Cellular Assembly Stoichiometry of Polycomb Complexes on Chromatin Revealed by Single-molecule Chromatin Immunoprecipitation Imaging

Epigenetic complexes play an essential role in regulating chromatin structure, but information about their assembly stoichiometry on chromatin within cells is poorly understood. The cellular assembly stoichiometry is critical for appreciating the initiation, propagation, and maintenance of epigenetic inheritance during normal development and in cancer. By combining genetic engineering, chromatin biochemistry, and single-molecule fluorescence imaging, we developed a novel and sensitive approach termed single-molecule chromatin immunoprecipitation imaging (Sm-ChIPi) to enable investigation of the cellular assembly stoichiometry of epigenetic complexes on chromatin. Sm-ChIPi was validated by using chromatin complexes with known stoichiometry. The stoichiometry of subunits within a polycomb complex and the assembly stoichiometry of polycomb complexes on chromatin have been extensively studied but reached divergent views. Moreover, the cellular assembly stoichiometry of polycomb complexes on chromatin remains unexplored. Using Sm-ChIPi, we demonstrated that within mouse embryonic stem cells, one polycomb repressive complex (PRC) 1 associates with multiple nucleosomes, whereas two PRC2s can bind to a single nucleosome. Furthermore, we obtained direct physical evidence that the nucleoplasmic PRC1 is monomeric, whereas PRC2 can dimerize in the nucleoplasm. We showed that ES cell differentiation induces selective alteration of the assembly stoichiometry of Cbx2 on chromatin but not other PRC1 components. We additionally showed that the PRC2-mediated trimethylation of H3K27 is not required for the assembly stoichiometry of PRC1 on chromatin. Thus, these findings uncover that PRC1 and PRC2 employ distinct mechanisms to assemble on chromatin, and the novel Sm-ChIPi technique could provide single-molecule insight into other epigenetic complexes.     

The role and mechanisms of polycomb repressive complex 2 on the regulation of osteogenic and neurogenic differentiation of stem cells

The stem cells differentiate into osteoblasts or neurocytes is the key process for treatment of bone‐ or neural tissue‐related diseases which is caused by ageing, fracture, injury, inflammation, etc Polycomb group complexes (PcGs), especially the polycomb repressive complex 2 (PRC2), act as pivotal epigenetic regulators by modifying key developmental regulatory genes during stem cells differentiation. In this review, we summarize the core subunits, the variants and the potential functions of PRC2. We also highlight the underlying mechanisms of PRC2 associated with the osteogenic and neurogenic differentiation of stem cells, including its interaction with non‐coding RNAs, histone acetyltransferases, histone demethylase, DNA methyltransferase and polycomb repressive complex 1. This review provided a substantial information of epigenetic regulation mediated by PRC2 which leads to the osteogenic and neurogenic differentiation of stem cells.