The ETS-domain transcription factors Elk-1 and SAP-1 exhibit differential DNA binding specificities.
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.
Shore
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P
Department of Biochemistry and Genetics, Medical School, University of Newcastle upon Tyne, UK.
Sharrocks
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AD
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D016384:Consensus Sequence; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D050783:Proto-Oncogene Proteins c-ets; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism; D013379:Substrate Specificity; D014157:Transcription Factors / Q000378:metabolism; D050807:ets-Domain Protein Elk-1; D050808:ets-Domain Protein Elk-4
D017931:DNA Primers; D004268:DNA-Binding Proteins; C494112:ELK1 protein, human; C494193:ELK4 protein, human; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D050807:ets-Domain Protein Elk-1; D050808:ets-Domain Protein Elk-4; D004247:DNA