Nucleic Acids Research, 1989, Vol. 17, No. 16 6681-6691
© 1989
MOLECULAR BIOLOGY |
The deletion of the distal CCAAT box region of the A
-globin gene in Mack HPFH abolishes the binding of the erythroki specific protein NFE3 and of the CCAAT displacement protein
Dipartimento di Geoetica e di Biologia dei Microrganismi Milan, Italy 1Institut für Molekulare Pathologic Dr. Bohr-Gasse, A1030 Wien, Austria 2Department of Cell and Molecular Biology, Medical College of Georgia Augusta, GA 30912-2100, USA
Received April 19, 1989. Revised July 3, 1989. Accepted July 21, 1989.
Non-deletion Hereditary Persistence of Fetal Hemoglobin (HPFH) Is characterized by great elevation of the synthesis, In adult age, of fetal hemoglobin (HbF), of either the A
or G type. Strong genetic evidence Indicates point mutations In the G or A -globln promoter as responsible for overexpresston of the mutated gene. Here we report that a 13 nucleotkles deletion In the CCAAT box region of the A -globln promoter, associated with greater than 100 fold overexpresston of the gene, abolishes the In vitro binding of the ubiquitous factors CP1 and COP (CCAAT displacement protein) and of the erythroW specific protein NFE3. Loss of NFE3 binding Is consistent with a simlar effect of the -117 G - A HPFH mutation, suggesting a possible role of NFE3 as a negatively acting factor. In addition, Ices of CDP binding Indicates that this alteration might also contribute to the HPFH phenotype In this particular case, suggesting possible heterogeneity of the mechanisms causing HPFH.
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