Watt P, Lamb P, Squire L, Proudfoot N
Sir William Dunn School of Pathology, University of Oxford, UK.
Nucleic Acids Res. 1990 Mar 25;18(6):1339-50. doi: 10.1093/nar/18.6.1339.
We describe the characterisation of cis-acting sequences which control the tissue specific expression of the human zeta globin gene. An extensive search for enhancer sequences in the vicinity of this gene proved negative. Instead our data demonstrate that the minimal promoter of the zeta gene is itself tissue specific. Sequences close to and possibly including the -100 CACCC and -70 CCAAT boxes display some erythroid specificity. However the principal tissue specific element is a GATAA sequence at -120 directly adjacent to the minimal promoter. Specific deletion of GATAA reduces zeta promoter activity 5 fold in erythroid but not non-erythroid cells. We also demonstrate that an erythroid specific factor binds to this GATAA sequence. Furthermore this factor forms a complex with the transcription factor CP1 which we show interacts with the zeta CCAAT box. We present evidence that the zeta GATAA binding factor is equivalent to GF1 recently purified and cloned by Tsai et al [1]. The erythroid specific GATAA sequence has been found in the promoters and enhancers of a number of erythroid specific genes. Similarly we show here that the zeta globin gene relies on a GATAA sequence in its promoter to specify its expression in erythroid cells.
我们描述了控制人类ζ珠蛋白基因组织特异性表达的顺式作用序列的特征。对该基因附近增强子序列的广泛搜索结果为阴性。相反，我们的数据表明，ζ基因的最小启动子本身具有组织特异性。靠近并可能包括-100 CACCC和-70 CCAAT框的序列表现出一些红系特异性。然而，主要的组织特异性元件是位于-120处与最小启动子直接相邻的GATAA序列。特异性缺失GATAA会使红系细胞中ζ启动子活性降低5倍，而非红系细胞中则不会。我们还证明，一种红系特异性因子与该GATAA序列结合。此外，该因子与转录因子CP1形成复合物，我们发现CP1与ζ CCAAT框相互作用。我们提供证据表明，ζ GATAA结合因子等同于Tsai等人[1]最近纯化和克隆的GF1。在许多红系特异性基因的启动子和增强子中都发现了红系特异性GATAA序列。同样，我们在此表明，ζ珠蛋白基因在其启动子中依赖GATAA序列来确定其在红系细胞中的表达。
