Read the full paper: Drosophila Rumpelstiltskin regulates Polycomb cis and trans interactions and Homie barrier activity

Chromatin states are a functional readout of combinatorial PTMs of histone tails. To decipher chromatin states underlying the medulloblastoma subgroups, we profiled a core set of six histone PTMs through chromatin immunoprecipitation coupled with sequencing (ChIP–seq): H3 lysine 4 monomethylation (H3K4me1; enhancer mark); H3 lysine 4 trimethylation (H3K4me3; promoter mark); H3 lysine 27 trimethylation (H3K27me3; Polycomb mark); H3 lysine 27 acetylation (H3K27ac; enhancer/promoter mark); H3 lysine 9 trimethylation (H3K9me3; heterochromatin mark); and H3 lysine 36 trimethylation (H3K36me3; transcription mark)18. Using 52 fresh–frozen tumor specimens representing each of the consensus medulloblastoma subgroups (WNT, n = 2; SHH, n = 5; Group 3, n = 19; Group 4, n = 26), 254 histone PTM ChIP–seq experiments were performed (H3K4me1, H3K4me3, H3K27me3 and H3K27ac, n = 52 tumors per mark; H3K9me3 and H3K36me3, n = 23 tumors per mark), of which 229 ChIP–seq profiles were newly generated as part of this study (Supplementary Table 1). Histone ChIP–seq profiles were integrated with mutational (n = 223)6, DNA methylation (n = 223)6 and RNA sequencing (RNA-seq; n = 167)6,8 datasets, which include most samples in the ChIP–seq cohort (Fig. 1a, Extended Data Fig. 1a and Supplementary Table 2). Histone modification tracks accurately recapitulate active chromatin...

Abstract. Polycomb repressive complex 1 (PRC1) forms nuclear condensates that organize target chromatin domains. SUMOylation modulates PRC1 clustering, but

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Neville, Ferguson et al. show that non-canonical Polycomb repressive complex 1.1-mediated gene silencing is antagonized by DOT1L and is required for the therapeutic efficacy of Menin and DOT1L inhibitors in mixed-lineage leukaemia.

Distal regulatory elements (DREs), such as enhancers, can regulate genes across megabase-long distances, presumably via coming into close spatial proximity. The establishment of new transcriptional programmes during cell type transitions is associated with widespread rewiring of the spatial organisation of the genome, including gain and loss of chromatin interactions. Extensive effort has been invested into understanding how chromatin interactions are formed during development, yet the mechanisms underlying their developmental loss remain largely unclear. By leveraging chromatin accessibility-assisted footprinting, acute protein degradation and chromatin conformation capture, we show that loss of promoter interactions cannot be explained by reduced binding of sequence-specific transcription factors (TFs). Instead, we identify a subset of interactions that depend on cohesin for programmed developmental disruption. These sites are characterized by high Polycomb enrichment and TF occupancy and engage in strong long-range interactions that undergo extensive differentiation-dependent rewiring. Preventing interaction loss by acute cohesin degradation results in the preferential downregulation of associated genes. Together, these results suggest that cohesin indirectly regulates developmental loss of Polycomb interactions by enabling the acquisition of other potentially regulatory contacts in a process that may shape transcriptional programs during cell type transitions. ### Competing Interest Statement The authors have declared no competing interest. European Research Council Helmholtz Society, VH-NG-1604

Canonical Polycomb repressive complex 1 (cPRC1) preserves cell fate decisions by repressing aberrant transcription of developmental regulator genes. We report the cryo-electron microscopy structure of the human cPRC1 holocomplex assembled from RING1B, BMI1, PHC2 and CBX7 bound to an H3K27me3-modifie …

Nature Structural & Molecular Biology, Published online: 14 September 2026; doi:10.1038/s41594-026-01885-6Ciapponi et al. determine the cryo-electron microscopy structure of the canonical Polycomb repressive complex 1 holocomplex and show how its architecture coordinates complex assembly, H2A monoubiquitination and genomic targeting.

The development of multicellular organisms relies on the precise establishment and stable inheritance of cell type-specific transcriptional programs without changes to the underlying DNA sequence. Polycomb group (PcG) proteins are evolutionarily conserved epigenetic repressors that govern developmen …

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Nature Structural & Molecular Biology, Published online: 14 September 2026; doi:10.1038/s41594-026-01885-6Ciapponi et al. determine the cryo-electron microscopy structure of the canonical Polycomb repressive complex 1 holocomplex and show how its architecture coordinates complex assembly, H2A monoubiquitination and genomic targeting.

Abstract. Polycomb repressive complex 1 (PRC1) forms nuclear condensates that organize target chromatin domains. SUMOylation modulates PRC1 clustering, but