Fetal hemoglobin production in adult baboons by 5-azacytidine or by phenylhydrazine-induced hemolysis is associated with hypomethylation of globin gene DNA.
Nucleoside analog were used to stimulate fetal hemoglobin synthesis in baboons. Only those nucleoside analogs (5-azacytidine and 2'-deoxy-5-azacytidine) that blocked DNA methylation caused large increases in Hb F levels. DNA extracted from bone marrow samples of these animals was cleaved with MspI or HpaII restriction enzymes and analyzed by Southern blot hybridization. Results of these experiments strongly support the hypothesis that hypomethylation of CCGG sequences in the gamma-gene region is a condition of gamma-gene expression. This also applies to Hb F elevations resulting from erythropoietic stress due to phenylhydrazine-induced hemolytic anemia.
D000818:Animals; D001374:Azacitidine / Q000494:pharmacology*; D005319:Fetal Hemoglobin / Q000235:genetics*; D005786:Gene Expression Regulation; D005796:Genes; D005914:Globins / Q000235:genetics*; D006461:Hemolysis; D008745:Methylation; D010215:Papio; D010659:Phenylhydrazines / Q000494:pharmacology*; D013997:Time Factors
D010659:Phenylhydrazines; C030299:phenylhydrazine; D005914:Globins; D005319:Fetal Hemoglobin; D001374:Azacitidine