Dhar V, Nandi A, Schildkraut C L, Skoultchi A I
Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York 10461.
Mol Cell Biol. 1990 Aug;10(8):4324-33. doi: 10.1128/mcb.10.8.4324-4333.1990.
Recent evidence suggests that DNA sequences from the region lying 5' of the human epsilon-globin gene are important for erythroid-specific expression of human beta-like globin genes. This region, as well as a region 20 kilobases (kb) downstream from the beta-globin gene, contains a set of developmentally stable, DNase I-superhypersensitive sites that are thought to reflect a chromatin structure supporting active globin gene expression. We have analyzed the chromatin structure in these two regions in a wide variety of nonerythroid and erythroid cells. The study included analysis of chromatin structure changes occurring during globin gene activation in mouse erythroleukemia-human nonerythroid cell hybrids. The results identified a hypersensitive site (III) 14.8 kb upstream of the epsilon-globin gene that was strictly correlated with active globin gene transcription. Interestingly, a multipotent human embryonal carcinoma cell line exhibited a hypersensitive site (IV) 18.4 kb upstream of epsilon-globin that was absent in all other nonerythroid cells examined, suggesting that chromatin structure changes at specific hypersensitive sites during embryonic development may also be important in globin gene repression.
最近的证据表明，人类ε-珠蛋白基因5'端区域的DNA序列对于人类β-样珠蛋白基因的红系特异性表达很重要。该区域以及β-珠蛋白基因下游20千碱基（kb）的区域包含一组发育稳定的、对DNase I高度敏感的位点，这些位点被认为反映了支持活跃珠蛋白基因表达的染色质结构。我们分析了多种非红系和红系细胞中这两个区域的染色质结构。该研究包括对小鼠红白血病-人类非红系细胞杂交体中珠蛋白基因激活过程中发生的确染色质结构变化的分析。结果确定了ε-珠蛋白基因上游14.8 kb处的一个超敏感位点（III），它与活跃的珠蛋白基因转录严格相关。有趣的是，一种多能人类胚胎癌细胞系在ε-珠蛋白上游18.4 kb处表现出一个超敏感位点（IV），在所检测的所有其他非红系细胞中均不存在，这表明胚胎发育过程中特定超敏感位点处的染色质结构变化在珠蛋白基因抑制中可能也很重要。
