Figure 2 | Scientific Reports

Figure 2

From: Etiology matters – Genomic DNA Methylation Patterns in Three Rat Models of Acquired Epilepsy

Figure 2

Differentially methylated regions and their distribution in three models of epilepsy.

(a–c) - Unsupervised hierarchical cluster analysis of differential methylation in (a) amygdala stimulation, (b) TBI and (c) pilocarpine models. Hypermethylation – yellow, hypomethylation – blue, green – control, magenta - SE/TBI. (d) - Heatmap summarizing overlapping regions with consistent change in DNA methylation in at least 2 of 3 models of epilepsy (p < 0.01). Hypermethylation – yellow, hypomethylation – blue, green – control, magenta - SE/TBI. (e) - Rat genome ideogram summarizing the probability of increased (yellow) or decreased (blue) DNA methylation in injured vs. control animals in three animal epilepsy models. Outer ring represents chromosomes. Inner rings indicate location of methylation events in each model (amygdala stimulation - light blue, TBI - light green, pilocarpine - light red, hypermethylation – yellow, hypomethylation – blue). Distance from black line in the middle of each ring represents increasing probability of methylation change (presented as -log10 of p-value). Arrowheads indicate areas in chromosomes 6 and 15 that lacked increased methylation in the amygdala stimulation model. (f) - Rat genome ideogram summarizing DNA methylation changes common for pairs of models (inner gray rings). Outer ring represents chromosomes. Red bars - common increased methylation events, blue bars - common decreased methylation events. (g) - Venn diagram presenting differentially methylated DNA regions detected in each model of epilepsy and regions overlapping between models with change in methylation to the same direction. (h–j) - Genomic distribution of DNA methylation changes in (h) amygdala stimulation, (i) TBI and (j) pilocarpine models. Frequency of observed methylation changes compared with non-differentially methylated regions (p < 0.01), with upper and lower 95% confidence intervals for different genomic features. Magenta - increased methylation, green - decreased methylation, O/E - observed/expected ratio, CpG - CpG islands, SNP - single nucleotide polymorphism, TSS - transcriptional start site, UTR - untranslated region. (k) - Ratio of increased to decreased methylation events across genomic features for each epilepsy model with upper and lower 95% confidence intervals. Blue, green and light red bars represent the focal amygdala stimulation, TBI and systemic pilocarpine models, respectively. *p < 0.05, **p < 0.01, ***p < 0.001 (two-sided Fisher’s exact test).

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