Fig. 5
Gli regulates central carbon metabolism and methionine cycle flux through MDH2, and induces the methylation potential. a KEGG pathway analysis of differential metabolites in sh-Scr and sh-Scr+Gli (100 μM) groups. b KEGG pathway analysis of differential metabolites in sh-Mdh2 and sh-Mdh2+Gli (100 μM) groups. c Relative level of malic acid in different groups (n = 6). d Venn graph of differential metabolites in different groups (SC: sh-Scr; SG: sh-Scr+Gli (100 μM); RC: sh-Mdh2; RG: sh-Mdh2+Gli (100 μM)). Gli-regulated metabolites dependent on MDH2 were marked in orange font. e Relative p16INK4a level in MEFs treated with metabolites (100 μM) for 5 days. f Relative SAM, SAH, and SAM/SAH level in sh-Scr/sh-Mdh2 MRC-5 cells under different treatments. g Diagram of methionine cycle. h Relative H3K4me3, H3K9me3, and H3K27me3 level in MEFs treated with -/Gli (100 μM)/SAH (100 μM) for 1 day. i Quantification of h. j Relative H3K4me3, H3K9me3, and H3K27me3 level in MEFs treated with -/Gli (100 μM)/SAH (100 μM) for 5 days. k Quantification of j. l CUT&TAG-qPCR assays testing H3K4me3 and H3K27me3 level along the p16INK4a locus in MEFs treated with -/Gli (100 μM) for 5 days. Error bars represent the standard deviation (± SEM.). The significance of differences (*p < 0.05, **p < 0.01, ***p < 0.005) of all panels were analyzed with Tukey’s multiple comparisons tests
