An Inter-vascular Bed and Inter-species Investigation of Epigenetic Regulatory Elements in Endothelial Cells

Abstract

A major challenge in human genetics is to understand the mechanisms that control gene expression. To identify gene regulatory regions required for vascular homeostasis, we performed chromatin immunoprecipitation followed by DNA sequencing (ChIP-seq) for a variety of histone modifications and the JUN transcription factor in primary aortic endothelial cells (ECs) isolated from human, rat (Rattus norvegicus) and bovine (Bos taurus). We generated a chromatin state map for human aortic ECs and found that the vast majority of regulatory regions in aortic ECs were also active in venous ECs. By comparing the genomic occupancy of JUN and a histone modification indicative of active enhancers (H3K27ac) between species, we identified a set of conserved regulatory regions that were enriched for EC-specific pathways and human regulatory disease variants. Overall, we demonstrate that comparative epigenomics is a viable strategy to identify functionally important vascular gene regulatory elements.M.Sc.2018-11-09 00:00:0

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