Iron protoporphyrin IX (hemin) but not tin or zinc protoporphyrin IX can stimulate gene expression in K562 cells from enhancer elements containing binding sites for NF-E2

Abstract

Many genes whose transcription is erythroid-specific contain enhancer or promoter elements that bind the transcription factor NF-E2. Hemin induction increases the expression of globin genes in the human erythroleukemia cell line K562, and increases the expression of reporter genes regulated by enhancer elements containing binding sites for NF-E2. We sought to determine whether metalloporphyrins other than hemin can stimulate the transcriptional regulatory activity of enhancer elements containing binding sites for NF-E2. Aside from hemin, only cobalt protoporphyrin IX, to a limited extent, could increase the expression of reporter genes regulated by an enhancer element containing binding sites for NF-E2. The failure of metalloporphyrins other than hemin to stimulate the transient expression of a CAT reporter gene linked to an enhancer element containing a binding site for NF-E2 was correlated with their failure to induce benzidine-positive K562 cells and increase the steady-state level of γ-globin mRNA. This study suggests that elevated levels of zinc protoporphyrin IX found in the anemia of chronic disease, iron deficiency, and lead poisoning may contribute to a decrease in globin gene expression by interfering with the transcriptional activity of enhancer elements containing binding sites for NF-E2.