Nucleic Acids Research, 1990, Vol. 18, No. 9 2721-2731
© 1990
Molecular Biology |
A 46 base pair enhancer sequence within the locus activating region is required for induced expression of the gamma-globin gene during erythroid differentiation
Clinical Hematology Branch, National Heart Lung Blood Institute, National Institutes of Health Bethesda, MD 20892, USA
Received December 14, 1989. Accepted March 28, 1989.
The locus activating region (LAR), contained within 30 kb of chromatln flanking the human beta-globln 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 gammaglobin gene linked to LAR fragments was assayed in stably transfected K562 erythroleukemia cells. DNasel 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.
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