EACH HYPERSENSITIVE SITE OF THE HUMAN BETA-GLOBIN LOCUS-CONTROL REGION CONFERS A DIFFERENT DEVELOPMENTAL PATTERN OF EXPRESSION ON THE GLOBIN GENES

EACH HYPERSENSITIVE SITE OF THE HUMAN BETA-GLOBIN LOCUS-CONTROL REGION CONFERS A DIFFERENT DEVELOPMENTAL PATTERN OF EXPRESSION ON THE GLOBIN GENES
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DOI:
10.1101/gad.7.1.106
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发表时间:
1993-01-01
影响因子:
10.5
通讯作者:
GROSVELD, F
GROSVELD, F
中科院分区:
生物学1区
文献类型:
--
作者:
FRASER, P;PRUZINA, S;GROSVELD, F

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我们测试了珠蛋白基因座控制区(LCR)的单个DNase I高敏感部位(HS)区域对转基因小鼠中人γ和β基因发育表达模式的影响。结果表明,HS3是胚胎期最活跃的部位。它也是胎儿造血过程中唯一能够高水平表达伽马基因的位置,在一群同时能够表达伽马和贝塔基因的细胞中。HS4区在成虫期表现出最高的活性,而在胚胎期仅在低水平表达伽马基因。HS2在整个发育过程中驱动同等水平的伽马或β转基因表达。尽管HS1的活性很低,但HS1的模式与HS2相似。根据这些结果,我们得出结论,HS区域具有明显的发育特异性,并表明在完整的LCR中,它们相互作用形成更大的复合体,进而与珠蛋白基因相互作用。
We have tested the effect of the individual DNase I hypersensitive site (HS) regions of the globin locus control region (LCR) on the developmental expression pattern of the human gamma and beta genes in transgenic mice. The results show that HS3 is the most active site during the embryonic period. It is also the only site capable of high level expression of the gamma genes during fetal hematopoiesis, in a population of cells that are capable of expressing both the gamma and beta genes. Region HS4 shows the highest activity during the adult stage and expresses the gamma genes only at low levels during the embryonic period. HS2 drives equivalent levels of gamma or beta transgene expression throughout development. HS1 has a similar pattern to HS2, although the activity of HS1 is very low. From these results we conclude that the HS regions have distinct developmental specificities and suggest that in the complete LCR they interact with each other to form a larger complex which, in turn, interacts with the globin genes.