Extended Data Figure 3: Enhancer-driven TGF-β activity in Group 3 medulloblastoma.

This figure accompanies Fig. 2. a, Functional annotation of target genes assigned to subgroup-specific enhancers based on their significant overlap with gene sets annotated in Gene Ontology (GO Biological Process) and pathway databases (KEGG, Reactome). b, Waterfall plot discriminating the top 1,000 Group 3 and Group 4 subgroup-specific enhancers as defined by total H3K27ac signal. The distribution of assigned targets in Group 3, Group 4, and shared Group 3-4 targets are shown below the waterfall. c, Convergence of Group 3-specific enhancers on TGF-β pathway genes. Subgroup-specific enhancers are summarized as nodes according to their respective medulloblastoma enhancer class—Group 3, Group 4, and shared Group 3/Group 4—with edges representing individual enhancer/TGF-β pathway gene assignments. d, Amplification of the TGF-β type II receptor, ACVR2A, in a Group 3 medulloblastoma from the ChIP-seq cohort (MB-4M23). Log₂ read depth data (tumour versus matched germline) derived from WGS data for this case is shown (upper panel). Highly active H3K27ac enhancer peaks overlapping the amplified ACVR2A locus are shown for the same case (lower panel). e, Bar plot showing the difference in H3K27ac enhancer signal between MB-4M23 (ACVR2A-amplified Group 3 sample) and all other Group 3 samples. Bar plot shows H3K27ac log₂ fold change at all enhancers regulating TGF-β component genes. Enhancers are ranked by increasing change in H3K27ac. Error bars represent standard error of the mean fold change.