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.
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 reporters gene regulated by an enhancer elements 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 gamma-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.
Palma
J F
JF
Department of Medicine, State University of New York Health Science Center-Brooklyn 11203.
Gao
X
X
Lin
C H
CH
Wu
S
S
Solomon
W B
WB
D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D050981:Erythroid-Specific DNA-Binding Factors; D015870:Gene Expression / Q000187:drug effects*; D005914:Globins / Q000096:biosynthesis; D006427:Hemin / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive; D008665:Metalloporphyrins / Q000494:pharmacology*; D008969:Molecular Sequence Data; D050983:NF-E2 Transcription Factor; D050984:NF-E2 Transcription Factor, p45 Subunit; D011524:Protoporphyrins / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D014157:Transcription Factors / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D008665:Metalloporphyrins; D050983:NF-E2 Transcription Factor; D050984:NF-E2 Transcription Factor, p45 Subunit; C494692:NFE2 protein, human; D011524:Protoporphyrins; D012333:RNA, Messenger; D014157:Transcription Factors; C017803:zinc protoporphyrin; D006427:Hemin; D005914:Globins; C032628:tin protoporphyrin IX