Characterization of regulatory variants in promoters with enhancer activity and their relation with human diseases

Abstract

Gene regulation is driven by the interaction of regulatory sequences, commonly categorized as either enhancers or promoters. Recently, using a modification of the STARR- seq assay, we identified sets of promoters with enhancer potential. Given that the majority of genetic variants associated with human diseases and traits (93.7%) have been found to be located in noncoding DNA, in this follow up analysis we set out to characterize regulatory variants in ePromoters. Using genetic variants associated with traits and disease (GWAS catalog), we found a significant enrichment of GWAS variants associated to Hematological Measurements ePromoters found in HeLa. We hypothesize that genetic variants within ePromoters are likely to affect transcription factor (TF) binding. Therefore, we aimed to identify the relevant TFs interacting with these regulatory regions and look for variants disrupting TF binding. Particularly, we found variants affecting binding of TFs associated to inflammatory response. Understanding ePromoters and the regulatory mechanisms that affect their dual function will help identify the causes of human diseases and traits.