Drug response varies between individuals and can be caused by genetic factors. Nucleotide variation in gene regulatory elements can have a significant effect on drug response, but due to the difficulty in identifying these elements, they remain understudied. Here, we used various genomic assays to analyze human liver cells treated with or without the antibiotic rifampin and identified drug-induced regulatory elements genome-wide. The testing of numerous active promoters in human liver cells showed only a few to be induced by rifampin treatment. A similar analysis of enhancers found several of them to be induced by the drug. Nucleotide variants in one of these enhancers were found to alter its activity. Combined, this work identifies numerous novel gene regulatory elements that can be activated due to drug response and thus provides candidate sequences in the human genome where nucleotide variation can lead to differences in drug response. It also provides a universally applicable method to detect these elements for other drugs.
Vyšlo v časopise: Genome-Wide Discovery of Drug-Dependent Human Liver Regulatory Elements. PLoS Genet 10(10): e32767. doi:10.1371/journal.pgen.1004648 Kategorie: Research Article prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004648
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