title: Binding of nuclear factors to an upstream region of the human A gamma globin gene.
abstract: Two regions in the 5' flanking sequence of the human A gamma globin gene have been identified which bind nuclear factors. One of these regions is located between nucleotides -299 and -140 while the other lies between nucleotides -140 and -60. The former sequence is of interest as this region contains several mutations associated with non-deletion HPFHs. It is possible that factors responsible for the formation of these complexes are involved in developmental regulation of this gene. At the present time it is unknown whether this protein binds at or near the site of the mutations associated with HPFH. It is possible that a protein normally binds to this region in adult erythroid cells and represses expression of the gamma globin genes. When this sequence is altered the factor can not bind and expression of gamma globin genes in adult cells occurs. This could explain the continued production of fetal hemoglobin into adult life. In this model the sites of DNA-factor interaction include the nucleotides at -202, -198, -196 etc. such that nucleotide changes at these positions directly affect factor binding. Alternatively, the sites of DNA factor interaction may be sufficiently proximal to the -202 and -196 region such that single base change at -202, -198, and -196 cause perturbations in the DNA that indirectly effect the DNA-factor interaction. Careful footprinting must be carried out to define the exact binding site. The assay described here provides the basis for the purification of this factor and a study of its interaction with DNA.
mesh_terms: D001483:Base Sequence; D002467:Cell Nucleus / Q000378:metabolism*; D004262:DNA Restriction Enzymes; D005319:Fetal Hemoglobin / Q000235:genetics; D005796:Genes; D005809:Genes, Regulator; D005914:Globins / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data
chemical_list: D005914:Globins; D005319:Fetal Hemoglobin; D004262:DNA Restriction Enzymes