Figure 7. Cross-lineage enhancer co-option in metastatic ccRCC.

A, H3K27ac ChIP-seq signal in the orthologous mouse Mae-1 region. Black bar indicates Mae-1. B, Heatmap showing the activity of 294/314 MAEs in 111 physiological tissues from the Roadmap Epigenomics project. Column color code indicates normal tissue type, for a description of associated epigenetic states see Supplementary Figure 15B. Red bar highlights an enhancer module active in various lymphoid tissues. C, ENCODE p65 ChIP-seq data showing binding at the MAE-1 locus (black rectangle) in human lymphoblastoid cell lines. D, Model: Metastasis genes are activated via cross-lineage co-option of enhancer modules that collaborate with previously activated enhancers (grey peaks) to increase metastatic fitness.