Activation of Bmp2-Smad1 Signal and Its Regulation by Coordinated Alteration of H3K27 Trimethylation in Ras-Induced Senescence
Figure 2
Genes with H3K27me3 alteration.
(A) 284 Genes losing H3K27me3 mark, i.e. from >1.5 in MEFp2 to <1.0 in RasV12 cells (K27 column), were sorted by the fold expression change between MEFp2 and mean of RasV12 cells day3, 7, and 10 (Expression column). Upregulated genes were sorted upward (red). 30 genes losing H3K27me3 and gaining H3K4me3 simultaneously showed significant enrichment upward (Change K27→K4 column, †P = 0.000007, Kolmogorov-Smirnov test), e.g. p16. Bmp2 was found to be the most activated secreted factor among the 30 genes, and activated more than p16. Genes are listed in Table S3. 110 genes with bivalent modification in MEFp2 lost H3K27me3 and sustained H3K4me3 mark in RasV12 cells (Bi→K4), but did not show significant enrichment upward (P = 0.9). (B) 239 genes gaining H3K27me3 mark, i.e. from <1.0 in MEFp2 to <1.5 in RasV12 cells (K27 column). 189 genes had neither modification in MEFp2 (K27 column and K4 column), generally showed very low expression, and did not show significant enrichment downward (P = 1, (-)→K27). However, 9 genes gained H3K27me3 and lost H3K4me3 simultaneously, showed significant enrichment downward (K4→K27, *P = 0.0004), and included Smad6 and Nog. Genes were listed in Table S4.