Organization of promoter and enhancer elements. (A) Spatial arrangement and nucleotide sequences of the E-boxes (shaded) within the cloned human hepcidin gene promoter. Numbers indicate nucleotide positions with respect to the putative transcription initiation site, which is double-underlined.²¹  The partial prohepcidin open-reading frame is single-underlined. (B) Sequences of E-boxes (underlined) and proximal nucleotides in HepcP1.1-luc compared with a canonical USF site; R indicates purine; and Y, pyrimidine. A representative mouse hepcidin gene E-box (mhepcPE) is included for comparison. (C) Schematic of spatial organization of canonical (E-1 and E-2) and consensus (E-3 and E-4) E-boxes in the context of the promoter.