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.
MacLeod
M C
MC
Department of Carcinogenesis, University of Texas M.D. Anderson Cancer Center, Smithville 78957.
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