Cis-acting regulatory elements regulating CYP3A4 transcription in human liver.

ABSTRACT: The CYP3A4 enzyme is the most abundant drug-metabolizing enzyme in the liver, metabolizing ~50% of commonly used medications. CYP3A4 displays large interperson variability in expression and enzyme activity with unknown causes. This study aims to identify cis-acting regulatory elements controlling the transcription of CYP3A4, using chromatin conformation capture (4C and 3C assays), chromatin immunoprecipitation followed by quantitative PCR (ChIP-qPCR), clustered regularly interspaced short palindromic repeats (CRISPR)-mediated deletions of genomic regions and reporter gene assays in primary culture human hepatocytes and hepatic cell lines. 4C assays identified four regions (R1-R4) interacting with the CYP3A4 promoter, one of which overlaps with the previously identified upstream enhancers C

SUBMITTER: Collins JM 

PROVIDER: S-EPMC8457025 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature