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. Author manuscript; available in PMC: 2019 Feb 12.
Published in final edited form as: Cancer Cell. 2018 Feb 12;33(2):309–321.e5. doi: 10.1016/j.ccell.2018.01.008

Figure 3. Dissecting the nature of genes with promoter CpGI hypermethylation events in transformation and senescence.

Figure 3

(A) Top or middle Venn diagram shows comparison of promoter CpGI hypermethylated genes among HRAS_1, HRAS_2 and HRAS_3 or among Sen_1, Sen _2 and Sen _3. Bottom Venn diagram shows comparison of promoter CpGI hypermethylated genes between HRAS_all (all promoter CpGI hypermethylated genes from 3 HRAS replicates) and Sen_All (all promoter CpGI hypermethylated genes from 3 Sen replicates) and p-value was calculated by Fisher’s exact test. HSM, HRAS-Specific Methylated genes; SSM, Senescence-Specific Methylated genes; CM, Common Methylated genes.

(B) Simulation of independent stochastic methylation events shows the ratio of observed overlaps of genes methylated in each replicate of HRAS or HRAS_X and genes methylated in senescence compared to that of the expected overlaps of randomly selected genes with genes methylated in senescence. Slightly different numbers in Figure 3A and Figure 3B is because the overlaps in Figure 3A shows all CpGI genes while in Figure 3B only the CpGI genes present in the gene expression array were used. O:E indicates observed overlaps : expected overlaps.

(C) Gene Ontology (GO) analysis of HSM, SSM and CM genes. Heat map of −log10(p-values) is shown. Green stars indicate biological processes involved in cell development and differentiation.

(D) The methylation level (β value) of probes that are located nearby or within individual genes (CDH1 and SOX17) in EP (black), HRAS and HRAS_X (blue), and Sen (red) are shown. Early transformation-associated hypermethylated sites indicated in red rectangles; senescence-associated ones are in green rectangles.

See also Figure S3, Tables S1-S4.