MOLECULAR ANALYSIS OF THE HUMAN BETA-GLOBIN LOCUS ACTIVATION REGION
MOLECULAR ANALYSIS OF THE HUMAN BETA-GLOBIN LOCUS ACTIVATION REGION
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DOI：
10.1073/pnas.86.14.5439
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发表时间：
1989-07-01
影响因子：
11.1
通讯作者：
GROUDINE, M
中科院分区：
文献类型：
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作者：
FORRESTER, WC;NOVAK, U;GROUDINE, M
最近，含有四个红系特异性DNA序列的DNA序列在人ε-DNA的20个DNA酶5“内含有四个红系特异性DNA酶I超敏位点。珠蛋白基因被认为是一个重要的顺式调节元件，即基因座激活区（LAR）。LAR的亚片段，包含全部或仅两个5“或两个3”h超敏位点，与人β-HLA-A连接。珠蛋白基因，并分析它们对稳定转化的小鼠红白血病（MEL）细胞中珠蛋白基因表达的影响。含有所有四个超敏位点的构建体增加β-珠蛋白mRNA水平为8至13倍，而仅具有5“或3”位点的构建体在较小程度上增加珠蛋白表达。当在3 T3成纤维细胞中测定构建体时，没有观察到效果。所有LAR衍生物在诱导MEL细胞分化之前和之后在MEL细胞中的相应序列位置处形成超敏位点。然而，在3 T3成纤维细胞中，仅形成对应于先前描述的红细胞特异性-10.9位点的超敏位点。
Recently, DNA sequences containing four erythroid-specific DNA sequences containing four erythroid-specific DNase I hypersensitive sites within 20 kilobases 5'' of the human .epsilon.-globin gene have been identified as an important cis-acting regulatory element, the locus activation region (LAR). Subfragments of the LAR, containing either all or only the two 5'' or two 3'' h hypersensitive sites were linked to the human .beta.-globin gene and analyzed for their effect on globin gene expression in stably transformed mouse erythroleukemia (MEL) cells. Constructs containing all four of the hypersensitive sites increase .beta.-globin mRNA levels 8- to 13-fold, while constructs with only the 5'' or 3'' sites increase globin expression to a lesser extent. No effect was seen when the constructs were assayed in 3T3 fibroblasts. All of the LAR derivatives form hypersensitive sites at the corresponding sequence position in MEL cells prior to and after induction of MEL cell differentiation. However, in 3T3 fibroblasts only the hypersensitive site corresponding to the previously described erythroid-specific -10.9 site was formed.