Transcriptional regulation of renal organic anion transporter 1 by B‐cell CLL/lymphoma 6 (892.33)

Abstract

The human organic anion transporters 1 (OAT1) is crucial for the excretion of organic anions in renal proximal tubular cells and was classified as clinically relevant transporter in the kidneys. Our previous study indicated that renal male‐predominant expression of rat Oat1 and Oat3 appears to be regulated by transcription factor B‐cell CLL/lymphoma 6 (BCL6). The aim of this study was to characterize the effect of BCL6 on human OAT1 promoter.Luciferase assays were carried out on Opossum kidney (OK) cells transiently transfected with promoter constructs of OAT1 and expression vectors for BCL6. Transcription factor (TF) activation profiling plate array was used for monitoring the activation of multiple transcription factors in nuclear extracts of pcDNA3‐BCL6 and pcDNA3 transfected OK cells. The protein expression of several transcription factors was investigated using fluorescence microscopy and Western blot.BCL6 enhanced the promoter activity of OAT1, independently of predicted BCL6‐binding sites. Promoter sequence ‐63 to +1 bp of OAT1, which contained HNF1a binding sites, is the minimal regions required for BCL6 dependent activation. BCL6 enhanced the protein expression of HNF1α, a known OAT1 activator. HNF1α dependent activation of OAT1 promoter was increased by BCL6.BCL6 constitutes a promising candidate gene for the regulation of human OAT1 transcription, possibly via activation of HNF1α.