Identification of a DNA structural motif that includes the binding sites for Sp1, p53 and GA-binding protein.
We have analyzed predicted helical twist angles in the 21-bp repeat region of the SV40 genome, using a semi-empirical model previously shown to accurately predict backbone conformations. Unexpectedly, the pattern of twist angles characteristic of the six GC-boxes is repeated an additional five times at positions that are regularly interspersed with the six GC-box sequences. These patterns of helical twist angles are associated with a second, imperfectly-repeated sequence motif, the TR-box 5'-RRNTRGG. Unrelated DNA sequences that interact with trans-acting factors (p53 and GABP) exhibit similar twist angle patterns, due to elements of the general form 5'-RRRYRRR that occur as interspersed arrays with a spacing of 10-11 bp and an offset of 4-6 bp. Arrays of these elements, which we call pyrimidine sandwich elements (PSEs), may play an important role in the interaction of trans-acting factors with DNA control regions. In 13 human proto-oncogenes analyzed, we identified 31 PSE arrays, 11 of which were in the 5'-flanking regions of the genes. The most extensive array was found in the promoter region of the K-ras gene. Extending over 80 bp of DNA, it contained 16 PSEs that showed an average deviation from the SV40 criterion pattern of angles of only 1.2 degrees.
Department of Carcinogenesis, University of Texas M.D. Anderson Cancer Center, Smithville 78957.
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MacLeod
D001483:Base Sequence; D001665:Binding Sites; D004247:DNA / Q000235:genetics / Q000648:ultrastructure*; D004279:DNA, Viral / Q000235:genetics / Q000648:ultrastructure; D004268:DNA-Binding Proteins / Q000378:metabolism*; D051268:GA-Binding Protein Transcription Factor; D005786:Gene Expression Regulation; D006801:Humans; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009857:Oncogenes; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D012091:Repetitive Sequences, Nucleic Acid; D013539:Simian virus 40 / Q000235:genetics; D016329:Sp1 Transcription Factor / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D004279:DNA, Viral; D004268:DNA-Binding Proteins; D051268:GA-Binding Protein Transcription Factor; D012333:RNA, Messenger; D016329:Sp1 Transcription Factor; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D004247:DNA