Prohepcidin Binds to the HAMP Promoter and Autoregulates its Own Expression

In this study, we propose a novel role for prohepcidin in the regulation of its own transcription. Using indirect immunofluorescence and mCherry tagging, a portion of prohepcidin was detected in the nucleus of hepatocytes. Prohepcidin was found to specifically bind to the STAT3 site in the promoter of HAMP. Overexpression of prohepcidin in WRL68 cells decreased HAMP promoter activity, whereas decreasing the amount of prohepcidin caused increased promoter activity measured by luciferase reporter-gene assay. Moreover, overexpression of the known prohepcidin binding partner, alpha-1 antitrypsin caused increased HAMP promoter activity, suggesting that only the non-alpha-1 antitrypsin-bound prohepcidin affects the expression of its own gene. Our results indicate that prohepcidin can bind to and transcriptionally regulate the expression of HAMP, suggesting a novel autoregulatory pathway of hepcidin gene expression in hepatocytes.

Source: BJ Cell - February 7, 2013 Category: Biochemistry Authors: E Pandur, K Sipos, L Grama, J Nagy, V S Poór, G Sétáló Jr., A Miseta, Z Fekete Tags: BJ Cell Source Type: research