Gillemans N, Tewari R, Lindeboom F, Rottier R, de Wit T, Wijgerde M, Grosveld F, Philipsen S
Erasmus University Rotterdam, Medical Genetics Center-Department of Cell Biology, 3000 DR Rotterdam, The Netherlands.
Genes Dev. 1998 Sep 15;12(18):2863-73. doi: 10.1101/gad.12.18.2863.
The locus control region of the beta-globin cluster contains five DNase I hypersensitive sites (5'HS1-5) required for locus activation. 5'HS3 contains six G-rich motifs that are essential for its activity. Members of a protein family, characterized by three zinc fingers highly homologous to those found in transcription factor Sp1, interact with these motifs. Because point mutagenesis cannot distinguish between family members, it is not known which protein activates 5'HS3. We show that the function of such closely related proteins can be distinguished in vivo by matching point mutations in 5'HS3 with amino acid changes in the zinc fingers of Sp1 and EKLF. Testing their activity in transgenic mice shows that EKLF is a direct activator of 5'HS3.
β-珠蛋白基因簇的基因座控制区包含五个基因座激活所需的脱氧核糖核酸酶I高敏位点（5'HS1 - 5）。5'HS3包含六个对其活性至关重要的富含G的基序。一个蛋白质家族的成员，其特征是具有三个与转录因子Sp1中发现的锌指高度同源的锌指，与这些基序相互作用。由于点突变无法区分家族成员，因此尚不清楚哪种蛋白质激活5'HS3。我们表明，通过将5'HS3中的点突变与Sp1和EKLF锌指中的氨基酸变化相匹配，可以在体内区分此类密切相关蛋白质的功能。在转基因小鼠中测试它们的活性表明，EKLF是5'HS3的直接激活剂。
