A MAJOR POSITIVE REGULATORY REGION LOCATED FAR UPSTREAM OF THE HUMAN ALPHA-GLOBIN GENE LOCUS
A MAJOR POSITIVE REGULATORY REGION LOCATED FAR UPSTREAM OF THE HUMAN ALPHA-GLOBIN GENE LOCUS
复制标题
DOI：
10.1101/gad.4.9.1588
复制
发表时间：
1990-09-01
影响因子：
10.5
通讯作者：
AYYUB, H
中科院分区：
文献类型：
--
作者：
HIGGS, DR;WOOD, WG;AYYUB, H
我们已经确定了一个远程的、组织特异性的、积极的调节元件，它在确定人类α水平方面非常重要。-珠蛋白基因表达。稳定的转化子包含这个DNA片段连接到。α。小鼠红细胞中表达人α的基因。mRNA的水平与含有人类α的种间杂交体中所见的水平难以区分。16号染色体上正常情况下的基因。此外，所有含有。α。与该区域相关的基因表达。α。红系组织中-珠蛋白mRNA水平升高；在一只这样的老鼠身上，可以很容易地检测到人类α。外周血可见-珠蛋白链。这一区域在α上游的位置、结构和功能上有相当大的相似性。-球蛋白复合物与先前描述的。β。-珠蛋白显性控制区（DCR）这与两个基因簇之间的其他结构和功能差异形成鲜明对比。这些关键的正调控区域可能提供了目标序列，通过这些目标序列协调α的调控。-和。beta。类似珠蛋白的基因。
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 in 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.