The deletion of the distal CCAAT box region of the Aγ-globin gene in Mack HPFH abolishes the binding of the erythroki specific protein NFE3 and of the CCAAT displacement protein
- 1 January 1989
- journal article
- research article
- Published by Oxford University Press (OUP) in Nucleic Acids Research
- Vol. 17 (16), 6681-6691
- https://doi.org/10.1093/nar/17.16.6681
Abstract
No-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.gamma. or G.gamma. type. Strong genetic evidence indicates point mutations in the G.gamma.- or A.gamma.-globin promoter as responsible for overexpression of the mutated gene. Here we report that a 13 nucleotides deletion in the CCAAT box region of the A.gamma.-globin promoter, associated with greater than 100 fold overexpression of the gene, abolishes the in vitro binding of the ubiquitous factors CP1 and CDP (CCAAT displacement protein) and of the erythroid specific protein NFE3. Loss of NFE3 binding is consistent with a similar effect of the -117 G .fwdarw. A HPFH mutation, suggesting a possible role of NFE3 as a negatively acting factor. In addition, loss 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.Keywords
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