Peterson K R, Clegg C H, Navas P A, Norton E J, Kimbrough T G, Stamatoyannopoulos G
Division of Medical Genetics, Department of Medicine, University of Washington, Seattle 98195, USA.
Proc Natl Acad Sci U S A. 1996 Jun 25;93(13):6605-9. doi: 10.1073/pnas.93.13.6605.
To analyze the function of the 5' DNase I hypersensitive sites (HSs) of the locus control region (LCR) on beta-like globin gene expression, a 2.3-kb deletion of 5'HS3 or a 1.9-kb deletion of 5'HS2 was recombined into a beta-globin locus yeast artificial chromosome, and transgenic mice were produced. Deletion of 5'HS3 resulted in a significant decrease of epsilon-globin gene expression and an increase of gamma-globin gene expression in embryonic cells. Deletion of 5'HS2 resulted in only a small decrease in expression of epsilon-, gamma-, and beta-globin mRNA at all stages of development. Neither deletion affected the temporal pattern of globin gene switching. These results suggest that the LCR contains functionally redundant elements and that LCR complex formation does not require the presence of all DNase I hypersensitive sites. The phenotype of the 5'HS3 deletion suggests that individual HSs may influence the interaction of the LCR with specific globin gene promoters during the course of ontogeny.
为了分析β-类珠蛋白基因座控制区（LCR）5'端脱氧核糖核酸酶I高敏位点（HSs）对β-类珠蛋白基因表达的作用，将5'HS3的2.3kb缺失或5'HS2的1.9kb缺失重组到β-珠蛋白基因座酵母人工染色体中，并制备了转基因小鼠。5'HS3的缺失导致胚胎细胞中ε-珠蛋白基因表达显著降低，γ-珠蛋白基因表达增加。5'HS2的缺失仅导致发育各阶段ε-、γ-和β-珠蛋白mRNA表达略有下降。两种缺失均未影响珠蛋白基因转换的时间模式。这些结果表明，LCR包含功能冗余元件，并且LCR复合物的形成并不需要所有脱氧核糖核酸酶I高敏位点的存在。5'HS3缺失的表型表明，在个体发育过程中，单个HSs可能会影响LCR与特定珠蛋白基因启动子的相互作用。
