Higgs D R, Wood W G, Jarman A P, Sharpe J, Lida J, Pretorius I M, Ayyub H
Medical Research Council Molecular Haematology, John Radcliffe Hospital, Headington, Oxford, UK.
Genes Dev. 1990 Sep;4(9):1588-601. doi: 10.1101/gad.4.9.1588.
We have identified a remote, tissue-specific, positive regulatory element that is of major importance in determining the level of human alpha-globin gene expression. Stable transformants containing this DNA segment linked to the alpha gene in mouse erythroleukemia cells expressed human alpha mRNA at levels that are indistinguishable from those seen in interspecific hybrids containing the human alpha genes in their normal context on chromosome 16. Furthermore, all transgenic mice containing the alpha genes linked to this region expressed alpha-globin mRNA at high levels in erythroid tissues; and in one such mouse, readily detectable levels of human alpha-globin chains could be demonstrated in the peripheral blood. There is considerable similarity in the position, structure, and function of this region upstream of the alpha-globin complex with previously described elements within the beta-globin dominant control region (DCR). This is m marked contrast to other structural and functional differences between the two gene clusters. It seems likely that these critical, positive regulatory regions might provide target sequences through which coordinate regulation of the alpha- and beta-like globin genes is achieved.
我们已经鉴定出一个远距离的、组织特异性的正向调控元件，它在决定人类α-珠蛋白基因表达水平方面至关重要。在小鼠红白血病细胞中，含有与α基因相连的该DNA片段的稳定转化体所表达的人α mRNA水平，与在16号染色体上正常情况下含有人类α基因的种间杂种中所观察到的水平无法区分。此外，所有含有与该区域相连的α基因的转基因小鼠在红系组织中都高水平表达α-珠蛋白mRNA；在其中一只这样的小鼠的外周血中，可以检测到相当水平的人α-珠蛋白链。α-珠蛋白复合体上游这一区域在位置、结构和功能上与先前在β-珠蛋白显性控制区（DCR）中描述的元件有相当大的相似性。这与两个基因簇之间的其他结构和功能差异形成了鲜明对比。这些关键的正向调控区域似乎可能提供靶序列，通过这些序列实现α-和β-样珠蛋白基因的协同调控。
