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.

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The catalytic subunit of Polycomb Repressive Complex 2 (PRC2), EZH2, is recurrently mutated in 25% of diffuse large B-cell lymphomas (DLBCL), causing increased H3K27me3 and decreased H3K27me2 levels. ...

Marin et al. report the role of lamin proteins and the lamin B receptor (LBR) in chromatin positioning at the nuclear periphery. Knockout of all lamins and LBR in mouse embryonic stem cells leads to h...

Embryonic development typically requires precise coordination among cells to achieve reproducible outcomes, leading to the assumption that cellular heterogeneity must be minimized or buffered against....

Challenging the prevailing view that H1 linker histones represent a general feature of repressed chromatin, Matthews et al. show a specific requirement for H1 in epigenetic repression by PRC2. Ablation of the H1 activator CRAMP1 results in linker histone insufficiency and derepression of PRC2 target genes.

Lagan, Gannon, et al. reveal that H3K27M-DMGs depend on a specific form of cPRC1 containing CBX4 and PCGF4. H3K27M alters H3K27me3 distribution, causing increased binding of CBX4-PCGF4-cPRC1 and oncogenic gene repression. CBX4’s ability to read H3K27me3 and to form a specific cPRC1 complex with PCGF4 makes it essential in DMG.

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Zijlmans and Stelloo et al. profiled in vivo proximal interactomes of PRC1 and PRC2 in mouse embryonic stem cells, identifying >100 proteins, including transcription factors and RNA-binding proteins. Their findings reveal shared and distinct roles of…

Porazzi et al. highlight how inhibiting the epigenetic regulators EZH2 and EZH1 enhances cancer cell immunogenicity, boosting the effectiveness of CAR- and TCR-engineered T cells across liquid and solid tumor models, which represents a promising strategy…

Losing parental histones during DNA replication fork passage challenges differentiation competence and cell viability.

Structures reveal that histone H3K36me3 and H3K4me3 modifications reduce Polycomb repressive complex 2 (PRC2) function through the inhibition of histone tail engagement and antagonistic binding to the...

Lack of understanding of cancer underlies harmful pseudoscience that circulates rampantly

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