Regulation of the ferrochelatase gene expression during differentiation of mouse erythroleukemia cells

Ferrochelatase [EC 4.99.1.1], the last step enzyme of heme biosynthesis, is transcribed from a single promoter. The enzyme is ubiquitously expressed in all cells, while the transcription is induced during erythroid differentiation. In a transient transfection assay, we identified two cis-acting elements involved in regulating the human ferrochelatase gene in mouse erythroleukemia (MEL) cells; one is the distal region (-108 to -95) for the basic expression in erythroid and non-erythroid cells, and the other is the proximal region (-80 to -72) corresponding to the induced expression during differentiation of dimethylsulfoxide-treated MEL cells. DNase I footprinting and gel mobility shift analyses revealed the presence of nuclear protein binding to the distal and the proximal regions, in both induced and uninduced MEL cells. These mean that two promoter regions play an important role in regulating the induced expression of ferrochelatase.