A 46 base pair enhancer sequence within the locus activating region is required for induced expression of the gamma-globin gene during erythroid differentiation.
The locus activating region (LAR), contained within 30 kb of chromatin flanking the human beta-globin gene cluster, has recently been shown to be essential for high level beta-globin gene expression. To determine the effect of fragments containing LAR sequences on globin gene expression, mRNA from a marked gamma-globin gene linked to LAR fragments was assayed in stably transfected K562 erythroleukemia cells. DNaseI hypersensitive site II (HS II), located 10.9 kb upstream of the epsilon-globin gene, was required for high level gamma-globin gene expression. We also showed that a 46 bp enhancer element within HS II was necessary and sufficient for the increased gamma-globin gene expression observed with hemin induced erythroid maturation of K562 cells. These results localize a distant regulatory element important for activation of globin genes during human erythroid cell maturation.
Sorrentino
B
B
Clinical Hematology Branch, National Heart Lung Blood Institute, National Institutes of Health, Bethesda, MD 20892.
Ney
P
P
Bodine
D
D
Nienhius
A W
AW
D001483:Base Sequence; D015139:Blotting, Southern; D002454:Cell Differentiation; D003001:Cloning, Molecular; D004742:Enhancer Elements, Genetic; D004912:Erythrocytes / Q000166:cytology* / Q000378:metabolism; D005786:Gene Expression Regulation; D005796:Genes; D005914:Globins / Q000235:genetics*; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
D005914:Globins