The -175 T▸C mutation in the promoter of the Aγ- Gor γ-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 γ-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 γ-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.

Increased erythroid-specific expression of a mutated HPFH gamma-globin promoter requires the erythroid factor NFE-1 / S. Nicolis, A. Ronchi, N. Malgaretti, R. Mantovani, B. Giglioni, S. Ottolenghi. - In: NUCLEIC ACIDS RESEARCH. - ISSN 0305-1048. - 17:14(1989), pp. 5509-5516. [10.1093/nar/17.14.5509]

Increased erythroid-specific expression of a mutated HPFH gamma-globin promoter requires the erythroid factor NFE-1

R. Mantovani;
1989

Abstract

The -175 T▸C mutation in the promoter of the Aγ- Gor γ-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 γ-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 γ-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.
Gene Expression Regulation ; Mutation ; Promoter Regions, Genetic ; Adult ; Animals ; Base Sequence ; Cell Line ; Fetal Hemoglobin ; Globins ; HeLa Cells ; Hemoglobinopathies ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; Molecular Sequence Data ; Plasmids ; Transfection
Settore BIO/18 - Genetica
1989
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/239159
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