Increased erythrold-specific expression of a mutated HPFH γ-globin promoter requires the erythroid factor NFE-1
Increased erythrold-specific expression of a mutated HPFH γ-globin promoter requires the erythroid factor NFE-1
复制标题
突变 HPFH γ-珠蛋白启动子的红细胞特异性表达增加需要红细胞因子 NFE-1
DOI:
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发表时间:
1989
期刊:
影响因子:
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通讯作者:
S. Ottolenghi
中科院分区:
文献类型:
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作者:
S. Nicolis;A. Ronchi;Nicoletta Malgarctti;R. Mantovani;B. Giglioni;S. Ottolenghi
The -175 T greater than C mutation in the promoter of the A gamma- or G gamma-globin gene causes a 50-100 fold increase of the expression of the respective gene in adult erythroid cells (Hereditary Persistence of Fetal Hemoglobin). We show here that this mutation increases 3-9 fold the expression of a gamma-CAT reporter plasmid transfected into the erythroid cells K562, but not that of the same plasmid in non erythroid cells. The overexpression of the mutant is abolished by the mutation of the binding site for the erythroid specific factor NFE1; inactivation of the adjacent binding site for the ubiquitous factor OTF1 does not cause overexpression of the normal gamma-globin promoter. Previous results demonstrated that the -175 mutation slightly increases the in vitro binding of NFE1 and almost abolishes that of OTF1; the present functional data indicate that altered binding of NFE1, but not of OTF1, is responsible for the observed overexpression of the mutated promoter.