The effects of HPFH mutations in the human. gamma. -globin promoter on binding of ubiquitous and erythroid specific nuclear factors
- Universita di Milano, Milan (Italy)
Genetic evidence indicates that single point mutations in the {gamma}-globin promoter may be the cause of high expression of the mutated gene in the adult period (Hereditary Persistence of Fetal Hemoglobin, HPFH). Here the authors show that one of these mutations characterized by a T-C substitution at position 175 in a conserved octamer (ATGCAAAT) sequence, abolishes the ability of a ubiquitous octamer binding nuclear protein to bind a {gamma}-globin promoter fragment containing the mutated sequence; however, the ability of two erythroid specific proteins to bind the same fragment is increased three to five fold. DMS interference and binding experiments with mutated fragments indicate that the ubiquitous protein recognizes the octamer sequence, while the erythroid specific proteins B2, B3 recognize flanking nucleotides. Competition experiments indicate that protein B2 corresponds to an erythroid-specific protein known to bind to a consensus GATAG sequence present at several locations in {alpha}, {beta} and {gamma}-globin genes. Although the distal CCAAT box region of the {gamma}-globin gene shows a related sequence, an oligonucleotide including this sequence does not show any ability to bind the above mentioned erythroid protein. The {minus}117 G-A mutation also known to cause HPFH, and mapping two nucleotides upstream from the CCAAT box, greatly decreases the binding of the erythroid-specific, but not that of the ubiquitous protein, to the CCAAT box region fragment.
- OSTI ID:
- 7101223
- Journal Information:
- Nucleic Acids Research; (UK), Journal Name: Nucleic Acids Research; (UK) Vol. 16:16; ISSN 0305-1048; ISSN NARHA
- Country of Publication:
- United States
- Language:
- English
Similar Records
Transcriptional role of a conserved GATA-1 site in the human. var epsilon. -globin gene promoter
A fetal globin gene mutation in /sup A/. gamma. nondeletion hereditary persistence of fetal hemoglobin increases promoter strength in a nonerythroid cell
Related Subjects
59 BASIC BIOLOGICAL SCIENCES
CHEMICAL REACTIONS
CROSS-LINKING
DISEASES
DNA BASE TRANSITIONS
DNA SEQUENCING
GENE MUTATIONS
GENE REGULATION
GENE REPRESSORS
GLOBIN
HEREDITARY DISEASES
MUTATIONS
NUCLEIC ACIDS
NUCLEOPROTEINS
OLIGONUCLEOTIDES
ORGANIC COMPOUNDS
POLYMERIZATION
PROTEINS
STRUCTURAL CHEMICAL ANALYSIS