Shore P, Sharrocks A D
Department of Biochemistry and Genetics, Medical School, University of Newcastle upon Tyne, UK.
Nucleic Acids Res. 1995 Nov 25;23(22):4698-706. doi: 10.1093/nar/23.22.4698.
The ETS DNA-binding domain is conserved amongst many eukaryotic transcription factors. ETS-domains bind differentially to specific DNA sites containing a central GGA trinucleotide motif. The nucleotides flanking this motif define the binding specificity of individual proteins. In this study we have investigated binding specificity of the ETS-domains from two members of the ternary complex factor (TCF) subfamily, Elk-1 and SAP-1. The ETS DNA-binding domains of Elk-1 (Elk-93) and SAP-1 (SAP-92) select similar sites from random pools of double stranded oligonucleotides based on the consensus sequence ACCGGAAGTR. However, SAP-92 shows a more relaxed binding site selectivity and binds efficiently to a greater spectrum of sites than does Elk-93. This more relaxed DNA binding site selectivity is most pronounced in nucleotides located on the 3' side of the GGA motif. This differential DNA-binding specificity is also exhibited by longer TCF derivatives and, indeed by the full-length proteins. Our results suggest that the range of potential in vivo target sites for SAP-1 is likely to be greater than for Elk-1. We discuss our results in relation to other similar studies carried out with more divergent ETS-domains.
ETS DNA结合结构域在许多真核转录因子中是保守的。ETS结构域与含有中央GGA三核苷酸基序的特定DNA位点有不同的结合。该基序两侧的核苷酸决定了各个蛋白质的结合特异性。在本研究中，我们研究了三元复合因子（TCF）亚家族的两个成员Elk-1和SAP-1的ETS结构域的结合特异性。Elk-1（Elk-93）和SAP-1（SAP-92）的ETS DNA结合结构域基于共有序列ACCGGAAGTR从双链寡核苷酸的随机文库中选择相似的位点。然而，与Elk-93相比，SAP-92表现出更宽松的结合位点选择性，并且能更有效地结合更广泛的位点。这种更宽松的DNA结合位点选择性在GGA基序3'侧的核苷酸中最为明显。更长的TCF衍生物以及全长蛋白也表现出这种不同的DNA结合特异性。我们的结果表明，SAP-1在体内的潜在靶位点范围可能比Elk-1更大。我们将我们的结果与使用差异更大的ETS结构域进行的其他类似研究相关联进行讨论。
