Research Paper Volume 15, Issue 14 pp 6690—6709

Figure 5. Age-related diminution in the gene-to-gene disparity of transcriptional activity. (A) A comparison of the expression levels of 285 exonic sequences from 175 epi-driver genes in 2m, 6m, 12m, and 23m individual samples. The Q1 and Q3 quartile-level lines along with the mean levels are shown (dots in red). (B) A comparison of expression levels of 285 exonic sequences by age group. Variances are shown below. The expression level was assessed by comparing the PCR amplicon counts of mouse cDNA and rat gDNA (M/R ratio; see text for details). (C) Patterns of transcriptional drift for genes with low and high transcriptional activity. The expression levels of target genes in 2m samples were compared to those in 6m, 12, or 23m samples. The thick black arrows denote the direction of change in expression levels in low-expressing genes (left, ‘hyper-transcription’) and high-expressing genes (right, ‘hypo-transcription’) with age. Grey and blue lines represent the reference and trend lines, respectively. (D) Correlation between methylation loss and gene expression increase. The third quartile (Q3) methylation level, which decreases upon hypomethylation, was plotted against the first quartile (Q1) expression level in the same sample. The regression curve shows a significant negative correlation between these two variables (R²=0.72). (E) Correlation between methylation gain and gene expression decrease. The number of zero methylation sites, which decreases upon hypermethylation, was plotted against the Q3 expression level in the same sample. The regression curve shows a significant positive correlation between these two variables (R²=0.43). (F) No relationship between methylation change and expression change (23m/2m) in the epi-driver genes.