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Blood, 1 November 2007, Vol. 110, No. 9, pp. 3436-3437.
Prepublished online as a Blood First Edition Paper on July 20, 2007; DOI 10.1182/blood-2007-05-091108.
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Submitted May 18, 2007
Accepted July 12, 2007
The distal location of the iron responsive region of the hepcidin promoter
Jaroslav Truksa, Pauline Lee, Hongfan Peng, Jonathan Flanagan, and Ernest Beutler*
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA, United States
Department of Hematology, St. Jude Children's Research Hospital, Memphis, TN, United States
* Corresponding author; email: beutler{at}scripps.edu.
The response of hepcidin transcription to iron has been repeatedly documented in living mice, but it is difficult to demonstrate the response in ex vivo systems. We have hydrodynamically transfected mice with plasmid constructs comprised of a murine hepcidin 1 promoter and fragments of the promoter fused to a firefly luciferase reporter. This method enabled us to quantitate the response of the hepcidin promoter to short term feeding of a high iron diet to mice that have been maintained on an iron-deficient diet. We show that the region of the promoter between 1,600 bp and 1,800 bp upstream from the start of translation is essential for the response to iron. The promoter region between -260 and -1600 bp is not essential for the iron responsiveness of hepcidin promoter. The iron-responsive region that we have mapped is the same region required for the in vitro response of HepG2 cells to stimulation with bone morphogenetic proteins and differs from the LPS/IL-6 responsive area.
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