title: Increased Sp1 binding mediates erythroid-specific overexpression of a mutated (HPFH) gamma-globulin promoter.
abstract: The -198 T----C mutation in the promoter of the A gamma-globin gene increases 20-30 fold the expression of this gene in adult erythroid cells of patients (Hereditary Persistence of Fetal Hemoglobin, HPFH). We show here that this mutation creates a strong binding site, resembling a CACCC box, for two ubiquitous nuclear proteins, one of which is Sp1. The mutated promoter is four to five-fold more efficient than a normal gamma-globin promoter in driving expression of a CAT reporter plasmid when transfected into erythroid cells. The overexpression of the mutant is abolished by the introduction of an additional mutation disrupting the new binding site. No overexpression of the mutant is observed in non-erythroid cells, indicating that the ubiquitous factors bound on the mutated sequence must cooperate with erythroid specific factors.
authors: Dipartimento di Genetica e di Biologia dei Microrganismi, Università di Milano, Italy.
authors: A
authors: A
authors: Ronchi
authors: S
authors: S
authors: Nicolis
authors: C
authors: C
authors: Santoro
authors: S
authors: S
authors: Ottolenghi
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D001667:Binding, Competitive; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism*; D005319:Fetal Hemoglobin / Q000235:genetics*; D015870:Gene Expression; D005914:Globins / Q000235:genetics*; D006453:Hemoglobinopathies / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D011401:Promoter Regions, Genetic / Q000235:genetics*; D016329:Sp1 Transcription Factor; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D016329:Sp1 Transcription Factor; D014157:Transcription Factors; D005914:Globins; D005319:Fetal Hemoglobin