A05

Our genome-wide studies uncovered massive epigenetic alterations accompanied by transcriptome changes, which are causative for the key pathological features of pulmonary arterial hypertension (PAH). We hypothesize that the reprogrammed epigenome of PAH vascular cells results in an aberrant organization of higher-order chromatin and super-enhancers, thereby maintaining the persistently activated vascular cell phenotype. We now aim 1) to identify PAH-associated changes in the enhancer landscape and activities, 2) to map the three-dimensional chromatin interactome and enhancer-promoter associations in PAH, and 3) to assess the biological function of candidate enhancers in the acquisition of the hypertensive phenotype.