Evidence for coordinate epigenomic roles for CTCF and histone H3.3 in K27M diffuse midline gliomas [CUT&RUN]

In this context, we identified a key role for CTCF in maintaining H3K27me3 levels at bivalent domains, and demonstrated that the H3.3K27M mutation affects both CTCF localization and H3K27me3 at these regions.

We further characterized a functional interaction between H3.3 and CTCF in diffuse midline glioma cells, finding that the H3.3K27M mutation affects CTCF localization, leading to an expansion of CTCF-bound domains including a large number of ectopic CTCF binding sites found in H3.3K27M but not WT cells. We also found that CTCF knockdown increases cell viability in H3.3K27M cells, and affected the expression of a set of genes highly enriched in active chromatin states and likely important for some of the oncogenic properties of these cells.