Fig. 5: Loss of H3K36me leads to a redistribution of SUV39H1-mediated H3K9me3 from heterochromatic regions to euchromatin.
From: H3K36 Methylation as a Guardian of Epigenome Integrity
a Genome browser tracks illustrating regions of H3K9me3 loss in TKO mMSCs. b Scatterplots of 100kb-binned H3K9me3 signal, comparing parental against TKO mMSCs, and parental against H3K36M-OE Cal27—indicating the formation of two clusters: cluster A (regions that gain H3K9me3) and cluster B (regions that lose H3K9me3). c Genome browser tracks illustrating loss of large H3K9me3 domains in H3K36M-OE Cal27 cells. Cluster B regions (blue) and Cluster A regions (orange) are indicated. d Heatmaps centered on cluster A and B regions, illustrating loss of H3K9me3 in cluster B regions in H3K36M-OE Cal27 cells. e Heatmaps centered on cluster A and B regions illustrating a reduction in H3K9me3 (left heatmap) and SUV39H1 (right heatmap) signal within cluster B, whereas cluster A regions exhibit increased H3K9me3 and SUV39H1 enrichment in TKO mMSCs. f Genome browser tracks showing a redistribution of H3K9me3 from cluster B to cluster A regions in TKO mMSCs. Similarly, SUV39H1 is redistributed to cluster A regions, with reduced occupancy in cluster B regions in TKO mMSCs. g Aggregate plots centered on gene bodies stratified by gene expression levels, demonstrating enrichment of SUV39H1 in expressed genes in TKO mMSCs. h Heatmaps showing that in parental mMSCs, SUV39H1 overexpression (OE) modestly increased H3K9me3 in cluster A but remained primarily enriched in inactive cluster B regions. In TKO cells, following SUV39H1-OE, higher levels of H3K9me3 are found in both clusters, especially in cluster A. SUV39H1 knockdown (KD) primarily reduced H3K9me3 in cluster B of parental cells, while in TKO cells, depletion was similar in both clusters. i Barplots showing the percentage of H3K9me3 signal in cluster A and B regions, indicating that in mMSC parental cells, SUV39H1-KD decreases the signal in cluster B regions with a concomitant increase in cluster A. In TKO mMSCs, SUV39H1-KD reduces H3K9me3 levels evenly across both clusters, with no shift in signal proportion. Normalized signals were either MS-normalized (H3K9me3) or input-normalized (SUV39H1-Flag), as previously described. Source data are provided as a Source Data file.
