The beta-globin dominant control region: hypersensitive site 2.

The Dominant Control Region (DCR) of the human beta-globin gene locus consists of four strong hypersensitive sites (HSS) upstream of the epsilon-globin gene. Addition of these sites confers copy number dependent expression on the human beta-globin gene in murine erythroleukaemia cells and transgenic mice, at levels comparable with the endogenous mouse globin genes. We have shown previously that a 1.9 kb fragment comprising HSS 2 accounts for 40-50% of the full effect of the DCR. In this paper we describe a deletional analysis of HSS 2. We show that a 225 bp fragment is sufficient to direct high levels of expression of the human beta-globin gene which is copy number dependent and integration site independent. This 225 bp fragment overlaps the major region that is hypersensitive 'in vivo'. DNase I footprinting shows the presence of four binding sites for the erythroid specific protein NF-E1; the three other footprinted regions display a remarkable redundancy of the sequence GGTGG and bind a number of proteins including Sp1 and the CACC box protein. The significance of these results for the regulation of globin gene expression is discussed.     

人Daintain 基因5'调控区序列的生物信息学分析

目的：探讨人Daintain 基因5''调控区的序列特征。方法：利用在线软件BLAST、Neural Network Promoter Prediction、Promoter 2.0、Promoter SCAN、EMBOSS、CpG Island Searcher 和TF SEARCH预测人Daintain 基因启动子区域、CpG 岛分布和转录因子结 合位点。结果：人Daintain 基因5''调控区存在1 个CAAT盒。Daintain 基因可能存在6 个启动子位点,CpG岛可能位于216 bp 区 间( 23 ~ 238 bp)。评分85 分以上时,该序列存在251 个可能的转录因子结合位点;评分90 分以上时,该序列存在70 个可能的转 录因子结合位点;评分95 分以上时,该序列存在16个可能的转录因子结合位点;评分100 分以上时,该序列存在7 个可能的转 录因子结合位点;这些结合的转录因子基本是与免疫细胞增殖或性别发生有关。结论：人Daintain 基因5''调控区的生物信息学研 究表明其转录受甲基化和多种转录因子的调控,为研究Daintain 基因启动子的功能提供理论基础。