Beta-globin locus activation regions: conservation of organization, structure, and function.
Beta-globin locus activation regions: conservation of organization, structure, and function.
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β-珠蛋白位点激活区域：组织、结构和功能的保护。
DOI：
10.1073/pnas.87.21.8207
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发表时间：
1990
影响因子：
11.1
通讯作者：
Stamatoyannopoulos,G
中科院分区：
文献类型：
--
作者：
Li,QL;Zhou,B;Powers,P;Enver,T;Stamatoyannopoulos,G
人β-珠蛋白基因座激活区（LAR）包含四个红系特异性DNA酶I超敏位点（I-IV），认为其主要负责激活β-珠蛋白结构域并促进高水平红系特异性珠蛋白基因表达。我们鉴定了山羊β-珠蛋白LAR，测定了其序列的10.2个碱基，并证明了其在转基因小鼠中的功能。人类和山羊LARs共享6.5个与ε-珠蛋白基因启动子一样高度保守的同源序列。此外，这两个LARs的总体空间结构得到了保留。这些结果表明，LAR的功能相关区域很大，除了它们的一级结构之外，保守元件的空间关系对于LAR功能也很重要。
The human beta-globin locus activation region (LAR) comprises four erythroid-specific DNase I hypersensitive sites (I-IV) thought to be largely responsible for activating the beta-globin domain and facilitating high-level erythroid-specific globin gene expression. We identified the goat beta-globin LAR, determined 10.2 kilobases of its sequence, and demonstrated its function in transgenic mice. The human and goat LARs share 6.5 kilobases of homologous sequences that are as highly conserved as the epsilon-globin gene promoters. Furthermore, the overall spatial organization of the two LARs has been conserved. These results suggest that the functionally relevant regions of the LAR are large and that in addition to their primary structure, the spatial relationship of the conserved elements is important for LAR function.