In this issue, Lagan et al.1 apply genome-wide and tiling-scan CRISPR screens to uncover a key role for CBX4 and its central region in promoting the growth of diffuse midline glioma cells bearing the ...

Researchers have discovered an important molecular mechanism underlying diffuse midline glioma - an aggressive and currently incurable brain tumour that mostly affects children.

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.