Increased Sp1 binding mediates erythroid-specific overexpression of a mutated (HPFH) gamma-globulin promoter.

Nucleic Acids Research
A RonchiS Ottolenghi

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.

References

May 25, 1989·Nucleic Acids Research·F CatalaF Grosveld
Oct 16, 1989·Biochemical and Biophysical Research Communications·B GiglioniS Ottolenghi
Sep 25, 1987·Nucleic Acids Research·R A Hooft van HuijsduijnenD Mathis
Aug 1, 1984·Proceedings of the National Academy of Sciences of the United States of America·F S CollinsS M Weissman

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Citations

Nov 1, 1996·The International Journal of Biochemistry & Cell Biology·S M Jane, J M Cunningham
Oct 25, 1994·Proceedings of the National Academy of Sciences of the United States of America·U M KoivistoK Kontula
Jan 1, 1990·Annals of the New York Academy of Sciences·S OttolenghiB Giglioni
Apr 2, 2008·IUBMB Life·Laura Manca, Bruno Masala
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Apr 1, 1991·Molecular and Cellular Biology·G M Anderson, S O Freytag
Mar 1, 1993·Baillière's Clinical Haematology·W G Wood

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