Retroviral transfer of a human fetal globin gene carrying the -202 G gamma beta (+)-HPFH mutation into the human erythroleukemia line, KMOE.
The presence of point mutations at position -202 relative to the mRNA Cap site of both human fetal gamma-globin genes is linked with elevated fetal globin levels in adults. The question addressed in this study is whether the -202 mutation affects gamma-globin gene expression in the same manner as the -117 hereditary persistence of fetal hemoglobin (HPFH) A gamma-globin mutation. The -117 mutation was found to cause over-expression and confer inducibility of a retrovirally transferred gamma-globin gene in cytosine arabinoside (araC)-treated KMOE cells in an earlier study. In this study, fetal globin genes driven by either the normal G gamma or -202 HPFH G gamma-globin promoter were retrovirally transferred into human erythroid KMOE cells. The -202 HPFH mutation did not cause over-expression or confer inducibility of the transferred gamma-globin gene in araC-treated KMOE cells. Thus, the -202 HPFH mutation affects gamma-globin gene expression by a different mechanism than the -117 HPFH mutation. Furthermore, this study provides evidence against a general increasing of gamma-globin gene expression as might be expected from the -202 mutation altering binding of a ubiquitous factor such as Sp1.
Stoeckert
C J
CJ
Department of Anatomy, University of Pennsylvania School of Medicine, Philadelphia 19104.
D005319:Fetal Hemoglobin / Q000096:biosynthesis / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D005822:Genetic Vectors; D005914:Globins / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute / Q000235:genetics*; D009154:Mutation; D009363:Neoplasm Proteins / Q000096:biosynthesis; D011401:Promoter Regions, Genetic; D012315:RNA Caps / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D011994:Recombinant Proteins / Q000096:biosynthesis; D012190:Retroviridae / Q000235:genetics; D013789:Thalassemia / Q000235:genetics*; D014407:Tumor Cells, Cultured / Q000378:metabolism
D009363:Neoplasm Proteins; D012315:RNA Caps; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011994:Recombinant Proteins; D005914:Globins; D005319:Fetal Hemoglobin