Lowrey C H, Bodine D M, Nienhuis A W
Clinical Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892.
Proc Natl Acad Sci U S A. 1992 Feb 1;89(3):1143-7. doi: 10.1073/pnas.89.3.1143.
The human beta-like globin gene locus contains embryonic, fetal, and adult globin genes that are regulated in a developmentally timed, as well as a tissue-specific, manner. The locus control region (LCR), located 5' of the globin genes, is characterized by four erythroid-specific nuclease-hypersensitive sites within native chromatin. These sites contain the active elements of the LCR. The LCR establishes an active chromatin conformation across the globin locus and enhances globin gene expression in transfected erythroleukemia cells and transgenic mice. We have used 5' DNase I hypersensitive site (HS) 4 as a model to define the minimum elements necessary for site formation. We have identified a 101-base-pair fragment within 5' HS4 that is the active site-forming element. DNase I footprint and gel-mobility shift assays have identified binding sites for transcription factors AP-1/NF-E2, Sp-1, and GATA-1 within the HS-forming element. We conclude that HS formation, the characteristic feature of the LCR in nuclear chromatin, requires interaction between erythroid-specific and ubiquitous nuclear proteins.
人类β样珠蛋白基因座包含胚胎、胎儿和成体珠蛋白基因，这些基因以发育定时以及组织特异性的方式受到调控。位于珠蛋白基因5'端的基因座控制区（LCR），其特征是在天然染色质中有四个红系特异性核酸酶超敏位点。这些位点包含LCR的活性元件。LCR在整个珠蛋白基因座建立活跃的染色质构象，并增强转染的红白血病细胞和转基因小鼠中的珠蛋白基因表达。我们以5'端脱氧核糖核酸酶I超敏位点（HS）4为模型来确定位点形成所需的最小元件。我们在5' HS4内鉴定出一个101个碱基对的片段，它是活性位点形成元件。脱氧核糖核酸酶I足迹法和凝胶迁移率变动分析已在HS形成元件内鉴定出转录因子AP-1/NF-E2、Sp-1和GATA-1的结合位点。我们得出结论，HS形成是核染色质中LCR的特征性特征，需要红系特异性核蛋白和普遍存在的核蛋白之间的相互作用。
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