The organic cation transporter 1 (OCT1/SLC22A1) is strongly and specifically expressed in the human liver. Here we show that the hepatocyte nuclear factor HNF1 regulates OCT1 transcription and contributes to the strong, liver-specific expression of OCT1. Bioinformatic analyses revealed strong conservation of HNF1 binding motifs in an evolutionary conserved region (ECR) in intron 1 of the OCT1 gene. Electrophoretic mobility shift and chromatin immunoprecipitation assays confirmed the specific binding of HNF1 to the intron 1 ECR. In reporter gene assays performed in HepG2 cells, the intron 1 ECR increased SV40 promoter activity by 22-fold and OCT1 promoter activity by 13-fold. The increase was reversed when the HNF1 binding sites in the intron 1 ECR were mutated or the endogenous HNF1A expression was downregulated with small interfering RNA.
See article at J Pharmacol Exp Ther 2013, 347:181–192.
- Copyright © 2013 by The American Society for Pharmacology and Experimental Therapeutics