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1. A BEN-domain protein and polycomb complex work coordinately to regulate transcription

   https://doi.org/10.1080/21541264.2022.2105128  

   Kurniawan, Fredy; Prasanth, Supriya G. (May 2022, Transcription)
2. A Polycomb repressive complex is required for RNAi-mediated heterochromatin formation and dynamic distribution of nuclear bodies

   https://doi.org/10.1093/nar/gkaa1262  

   Xu, Jing; Zhao, Xiaolu; Mao, Fengbiao; Basrur, Venkatesha; Ueberheide, Beatrix; Chait, Brian T; Allis, C David; Taverna, Sean D; Gao, Shan; Wang, Wei; et al (January 2021, Nucleic Acids Research)

   Abstract Polycomb group (PcG) proteins are widely utilized for transcriptional repression in eukaryotes. Here, we characterize, in the protist Tetrahymena thermophila, the EZL1 (E(z)-like 1) complex, with components conserved in metazoan Polycomb Repressive Complexes 1 and 2 (PRC1 and PRC2). The EZL1 complex is required for histone H3 K27 and K9 methylation, heterochromatin formation, transposable element control, and programmed genome rearrangement. The EZL1 complex interacts with EMA1, a helicase required for RNA interference (RNAi). This interaction is implicated in co-transcriptional recruitment of the EZL1 complex. Binding of H3K27 and H3K9 methylation by PDD1—another PcG protein interacting with the EZL1 complex—reinforces its chromatin association. The EZL1 complex is an integral part of Polycomb bodies, which exhibit dynamic distribution in Tetrahymena development: Their dispersion is driven by chromatin association, while their coalescence by PDD1, likely via phase separation. Our results provide a molecular mechanism connecting RNAi and Polycomb repression, which coordinately regulate nuclear bodies and reorganize the genome. 

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3. Bending and looping of long DNA by Polycomb repressive complex 2 revealed by AFM imaging in liquid

   https://doi.org/10.1093/nar/gkaa073  

   Heenan, Patrick R; Wang, Xueyin; Gooding, Anne R; Cech, Thomas R; Perkins, Thomas T (February 2020, Nucleic Acids Research)

   Abstract Polycomb repressive complex 2 (PRC2) is a histone methyltransferase that methylates histone H3 at Lysine 27. PRC2 is critical for epigenetic gene silencing, cellular differentiation and the formation of facultative heterochromatin. It can also promote or inhibit oncogenesis. Despite this importance, the molecular mechanisms by which PRC2 compacts chromatin are relatively understudied. Here, we visualized the binding of PRC2 to naked DNA in liquid at the single-molecule level using atomic force microscopy. Analysis of the resulting images showed PRC2, consisting of five subunits (EZH2, EED, SUZ12, AEBP2 and RBBP4), bound to a 2.5-kb DNA with an apparent dissociation constant ($$K_{\rm{D}}^{{\rm{app}}}$$) of 150 ± 12 nM. PRC2 did not show sequence-specific binding to a region of high GC content (76%) derived from a CpG island embedded in such a long DNA substrate. At higher concentrations, PRC2 compacted DNA by forming DNA loops typically anchored by two or more PRC2 molecules. Additionally, PRC2 binding led to a 3-fold increase in the local bending of DNA’s helical backbone without evidence of DNA wrapping around the protein. We suggest that the bending and looping of DNA by PRC2, independent of PRC2’s methylation activity, may contribute to heterochromatin formation and therefore epigenetic gene silencing. 

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4. Sustained inactivation of the Polycomb PRC1 complex induces DNA repair defects and genomic instability in epigenetic tumors

   https://doi.org/10.1007/s00418-024-02302-z  

   Rawal, Chetan C; Loubiere, Vincent; Butova, Nadejda L; Gracia, Juliette; Parreno, Victoria; Merigliano, Chiara; Martinez, Anne-Marie; Cavalli, Giacomo; Chiolo, Irene (July 2024, Histochemistry and Cell Biology)

   Abstract Cancer initiation and progression are typically associated with the accumulation of driver mutations and genomic instability. However, recent studies demonstrated that cancer can also be driven purely by epigenetic alterations, without driver mutations. Specifically, a 24-h transient downregulation ofpolyhomeotic(ph-KD), a core component of the Polycomb complex PRC1, is sufficient to induce epigenetically initiated cancers (EICs) inDrosophila, which are proficient in DNA repair and characterized by a stable genome. Whether genomic instability eventually occurs when PRC1 downregulation is performed for extended periods of time remains unclear. Here, we show that prolonged depletion of PH, which mimics cancer initiating events, results in broad dysregulation of DNA replication and repair genes, along with the accumulation of DNA breaks, defective repair, and widespread genomic instability in the cancer tissue. A broad misregulation of H2AK118 ubiquitylation and to a lesser extent of H3K27 trimethylation also occurs and might contribute to these phenotypes. Together, this study supports a model where DNA repair and replication defects accumulate during the tumorigenic transformation epigenetically induced by PRC1 loss, resulting in genomic instability and cancer progression. 

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5. Reproductive Long Intergenic Noncoding RNAs Exhibit Male Gamete Specificity and Polycomb Repressive Complex 2-Mediated Repression

   https://doi.org/10.1104/pp.17.01269  

   Johnson, Cameron; Conrad, Liza J.; Patel, Ravi; Anderson, Sarah; Li, Chenxin; Pereira, Andy; Sundaresan, Venkatesan (July 2018, Plant Physiology)