Extended Data Fig. 7: K36M alters H3K36me2/3 deposition and gene expression.
From: H3K36 methylation maintains cell identity by regulating opposing lineage programmes
(a) Median H3K36me3 deposition at expressed genes (RPKM > 0.1, n = 10,251 for WT, n = 10,496 for K36M) of indicated expression quintiles for WT (left) and K36M (right) samples on day 4 of reprogramming (n = 2 biologically independent replicates were integrated for this analysis). (b) Median fold change of H3K36me3 density over gene bodies of differentially expressed genes (upregulated = red, downregulated = blue, n = 1,872) on day 4 (n = 2 biologically independent replicates were integrated for this analysis). (c) Fold change of gene expression (y axis) vs. fold change of H3K36me3 (x axis) between K36M and WT samples on day 4 of reprogramming (n = 2 biologically independent replicates were integrated for this analysis). (d) Representative gene tracks for H3K36me3 and RNA levels at mesenchymal gene Vim, epithelial gene Cdh1, and pluripotency gene Pou5f1 (n = 2 biologically independent replicates). (e) Profile plots of H3K36me2 at promoters, enhancers, and gene bodies (n = 2 biologically independent replicates were integrated for this analysis). (f) Profile plots of H3K36me2 and H3K27ac at H3K36me2 domains containing down- or upregulated enhancers (n = 2 biologically independent replicates were integrated for this analysis). (g) Representative tracks for Prrx1, a mesenchymal gene downregulated in K36M samples on day 4, Krt8, and Pou5f1, epithelial/pluripotency genes upregulated in K36M samples on day 4 (n = 2 biologically independent replicates). Putative regulatory elements highlighted in grey. (h) Gene ontology terms of genes closest to H3K36me2 domain-embedded enhancers that are differentially downregulated in K36M cells. Analysis and p values from geneontology.org. (i) Gene ontology terms of genes closest to H3K36me2 domain-embedded enhancers that are differentially upregulated in K36M cells. Analysis and p values from geneontology.org. (j) Dot plot representing enrichment of ENCODE data for differentially active enhancers within H3K36me2 domains. P values were determined by Fisher’s exact test.