Sorrentino B, Ney P, Bodine D, Nienhius A W
Clinical Hematology Branch, National Heart Lung Blood Institute, National Institutes of Health, Bethesda, MD 20892.
Nucleic Acids Res. 1990 May 11;18(9):2721-31. doi: 10.1093/nar/18.9.2721.
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.
定位于人类β-珠蛋白基因簇两侧30 kb染色质范围内的基因座激活区域（LAR），最近已被证明对β-珠蛋白基因的高水平表达至关重要。为了确定含有LAR序列的片段对珠蛋白基因表达的影响，在稳定转染的K562红白血病细胞中检测了与LAR片段相连的一个标记γ-珠蛋白基因的mRNA。位于ε-珠蛋白基因上游10.9 kb处的DNaseI超敏感位点II（HS II），是γ-珠蛋白基因高水平表达所必需的。我们还表明，HS II内一个46 bp的增强子元件对于在K562细胞经血红素诱导的红系成熟过程中观察到的γ-珠蛋白基因表达增加是必要且充分的。这些结果定位了一个在人类红系细胞成熟过程中对珠蛋白基因激活很重要的远距离调控元件。
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