Proton nuclear magnetic resonance longitudinal-relaxation-rate measurements have been used to investigate the molecular events that occur during the early stages of the polymerization process of sickle hemoglobin. The longitudinal relaxation rates (T1-1) of the C2 protons of 11 observable surface histidyl residues in normal human adult and sickle hemoglobin in the deoxy state were measured in 0...

We investigated the spatio-temporal profile of hemoglobin subunit expression in developing avascular tissues. Significant up-regulation of hemoglobin subunits was identified in microarray experiments comparing blastocyst inner cell masses with undifferentiated embryonic stem (ES) cells. Hemoglobin expression changes were confirmed using embryoid bodies (derived from in vitro differentiation of ...

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We have analyzed the synthesis of fetal hemoglobin (HbF) in the differentiated erythroid colonies produced by erythropoietin-responsive committed erythroid progenitors in plasma cultures of human marrow and peripheral blood. Two independent biochemical techniques. carboxymethyl-cellulose column chromatography of 3H-leucine-Iabeled globin. and polyacrylamide gel electrophoresis of 59Fe-labeled h...

A transition from fetal hemoglobin (HbF) to adult hemoglobin (HbA) normally occurs within a few months after birth. Increased production of HbF after this period of infancy ameliorates clinical symptoms of the major disorders of adult β-hemoglobin: β-thalassemia and sickle cell disease. The transcription factor BCL11A silences HbF and has been an attractive therapeutic target for increasing HbF...

The human β-globin locus contains the β-like globin genes (i.e. fetal γ-globin and adult β-globin), which heterotetramerize with α-globin subunits to form fetal or adult hemoglobin. Thalassemia is one of the commonest inherited disorders in the world, which results in quantitative defects of the globins, based on a number of genome variations found in the globin gene clusters. Hereditary persis...

The ontogenic switch from fetal to adult hemoglobin could result from discontinuous events, such as replacement of fetal erythroid progenitor cells by adult ones, or gradual modulation of the hemoglobin program of a single progenitor cell pool. The former would result in progenitors at midswitch with skewed fractional beta-globin synthesis programs, the latter in a Gaussian distribution. For th...

The greatly increased tetramer strength of liganded fetal hemoglobin compared with adult hemoglobin is shown by its 70-fold smaller tetramer-dimer dissociation constant. This property has been shown previously to be only partially caused by the 5-amino-acid differences at both types of interfaces in each hemoglobin. A major contributor to tetramer strengthening is the 18-amino-acid N-terminal A...

Erythropoietin production in response to hypoxic-hypoxia is markedly reduced in the newborn when compared to the adult rat. This response improves steadily with age and reaches adult values at about 4 wk. When animals of the same age are stimulated with anemic-hypoxia, considerably higher levels of erythropoietin are found. The erythropoietin level is proportional to the degree of anemia and in...

Stimulation of sheep erythropoietic progenitor cells by erythropoietin (epo) has been studied with regard to its effect on the pattern of hemoglobin production. An analysis of hemoglobin (Hb) synthesis in BFU-E- and CFU-E-derived colonies from fetuses either homozygous for HbA (AA) (homozygous also for the beta c gene responsible for HbC production) or HbB (BB) (lacking the beta c gene) indicat...