A potential regulatory region for the expression of fetal hemoglobin in sickle cell disease.
We describe a 0.5-kb region located 1.65 to 1.15 kb upstream of the G gamma fetal globin gene with three polymorphisms of erythroid and ubiquitous nuclear protein binding motifs (GATA, CRE, and a new protein binding site). These three polymorphisms result in high-affinity and low-affinity motifs for nuclear proteins, and are combined in four arrangements called pre-G gamma frameworks (pG gamma Fs). Each pG gamma F is linked with one of the major haplotypes of the beta-globin gene cluster observed in sickle cell disease (SCD) associated with different mean levels of hemoglobin F (Hb F) expression (P < .001). This strong linkage and the differing affinities suggest that this region may be involved in the modulation of Hb F expression in SCD.
Pissard
S
S
INSERM U.91 Hôpital Henri Mondor, Créteil, France.
Beuzard
Y
Y
D000755:Anemia, Sickle Cell / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D005319:Fetal Hemoglobin / Q000096:biosynthesis* / Q000235:genetics; D005809:Genes, Regulator; D008040:Genetic Linkage; D005914:Globins / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D008969:Molecular Sequence Data
D005914:Globins; D005319:Fetal Hemoglobin