Increased Sp1 binding mediates erythroid-specific overexpression of a mutated (HPFH) γ-globulin promoter
Open Access
- 25 December 1989
- journal article
- research article
- Published by Oxford University Press (OUP) in Nucleic Acids Research
- Vol. 17 (24) , 10231-10241
- https://doi.org/10.1093/nar/17.24.10231
Abstract
The ∼198 T→C mutation in the promoter of the A γ-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 Spl. The mutated promoter is four to five-fold more efficient than a normal γglobin 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.This publication has 33 references indexed in Scilit:
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