Fig. 5
From: Landscape of evolutionary arms races between transposable elements and KRAB-ZFP family
TRIM28 regulates the expression of LTR7_HERVH and nearby genes in hESCs. (a) log2 fold change in the expression of LTR7_HERVH copies in TRIM28 knockout (KO) hESCs compared to wild-type (WT) hESCs for each LTR7_HERVH subfamily. Colors represent different subfamilies. Statistical analyses were performed using the two-sided Wilcoxon signed-rank test on the normalized read counts of LTR7_HERVH copies in wild-type and TRIM28 KO hESCs. The statistical significance indicates a tendency for LTR7_HERVH subfamily to be upregulated or downregulated due to TRIM28 depletion. P-values were adjusted for multiple testing using the Benjamini–Hochberg procedure ***FDR < 0.001; n.s., not significant. (b) Relationship between perturbation due to TRIM28 deficiency and the heterochromatin state (9 Het) of LTR7_HERVH. The intensity of the color indicates an overlap with the heterochromatin state. Statistical testing was conducted using the two-sided Mann–Whitney U test. P-values were adjusted using the Benjamini–Hochberg procedure. *FDR < 0.05. (c) Proportion of differentially expressed genes (DEG) in nearby genes of each LTR7_HERVH subfamily. Box plots on the left and right show the proportions of downregulated and upregulated protein-coding genes among the nearby genes, respectively. Statistical analyses were conducted using the two-sided binomial test and compared with the proportion of DEGs in all genes. P-values were adjusted using the Benjamini–Hochberg procedure. *FDR < 0.05, **FDR < 0.01, ***FDR < 0.001. (d) Schematic model illustrating the effect of the evolutionary arms race between LTR7_HERVH and KRAB-ZFPs (left) on the regulatory landscape of LTR7_HERVH and nearby genes in hESCs (right). As a result of the evolutionary arms race between LTR7_HERVH and KRAB-ZFPs, older LTR7_HERVH subfamilies are silenced by KRAB-ZFPs and TRIM28, whereas younger subfamilies are activated by pluripotent TFs. Silencing older subfamilies prevents the aberrant activation of nearby genes, whereas younger subfamilies function as cell type-specific regulatory elements.
