Bender M A, Reik A, Close J, Telling A, Epner E, Fiering S, Hardison R, Groudine M
Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Blood. 1998 Dec 1;92(11):4394-403.
The most upstream hypersensitive site (HS) of the beta-globin locus control region (LCR) in humans (5' HS 5) and chickens (5' HS 4) can act as an insulating element in some gain of function assays and may demarcate a beta-globin domain. We have mapped the most upstream HSs of the mouse beta-globin LCR and sequenced this region. We find that mice have a region homologous to human 5' HS 5 that is associated with a minor HS. In addition we map a unique HS upstream of 5' HS 5 and refer to this novel site as mouse 5' HS 6. We have also generated mice containing a targeted deletion of the region containing 5' HS 5 and 6. We find that after excision of the selectable marker in vivo, deletion of 5' HS 5 and 6 has a minimal effect on transcription and does not prevent formation of the remaining LCR HSs. Taken together these findings suggest that the most upstream HSs of the mouse beta-globin LCR are not necessary for maintaining the beta-globin locus in an active configuration or to protect it from a surrounding repressive chromatin environment.
人类β-珠蛋白基因座控制区（LCR）最上游的超敏位点（HS）（5' HS 5）和鸡的（5' HS 4）在某些功能获得性实验中可作为绝缘元件，并且可能界定一个β-珠蛋白结构域。我们已绘制出小鼠β-珠蛋白LCR最上游的HSs图谱并对该区域进行了测序。我们发现小鼠有一个与人类5' HS 5同源的区域，该区域与一个较小的HS相关。此外，我们在5' HS 5上游绘制了一个独特的HS，并将这个新位点称为小鼠5' HS 6。我们还构建了含有靶向缺失包含5' HS 5和6区域的小鼠。我们发现在体内切除选择标记后，5' HS 5和6的缺失对转录的影响最小，并且不会阻止其余LCR HSs的形成。综合这些发现表明，小鼠β-珠蛋白LCR最上游的HSs对于将β-珠蛋白基因座维持在活性状态或保护其免受周围抑制性染色质环境的影响并非必需。
