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Binding of myc proteins to canonical and noncanonical DNA sequences.

Blackwell, T K and Huang, J and Ma, A and Kretzner, L and Alt, F W and Eisenman, R N and Weintraub, H (1993) Binding of myc proteins to canonical and noncanonical DNA sequences. Molecular and cellular biology, 13 (9). pp. 5216-5224. ISSN 0270-7306

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Using an in vitro binding-site selection assay, we have demonstrated that c-Myc-Max complexes bind not only to canonical CACGTG or CATGTG motifs that are flanked by variable sequences but also to noncanonical sites that consist of an internal CG or TG dinucleotide in the context of particular variations in the CA--TG consensus. None of the selected sites contain an internal TA dinucleotide, suggesting that Myc proteins necessarily bind asymmetrically in the context of a CAT half-site. The noncanonical sites can all be bound by proteins of the Myc-Max family but not necessarily by the related CACGTG- and CATGTG-binding proteins USF and TFE3. Substitution of an arginine that is conserved in these proteins into MyoD (MyoD-R) changes its binding specificity so that it recognizes CACGTG instead of the MyoD cognate sequence (CAGCTG). However, like USF and TFE3, MyoD-R does not bind to all of the noncanonical c-Myc-Max sites. Although this R substitution changes the internal dinucleotide specificity of MyoD, it does not significantly alter its wild-type binding sequence preferences at positions outside of the CA--TG motif, suggesting that it does not dramatically change other important amino acid-DNA contacts; this observation has important implications for models of basic-helix-loop-helix protein-DNA binding.

Item Type: Article or Abstract
Additional Information: This article is freely available in PubMed Central and at the journal's website.
PubMed ID: 8395000
PMCID: PMC360210
Grant Numbers: CA 20525
Keywords or MeSH Headings: Amino Acid Sequence; Animals; Base Sequence; Basic-Leucine Zipper Transcription Factors; Binding Sites; Binding, Competitive; DNA-Binding Proteins/metabolism; Leucine Zippers; Molecular Sequence Data; Muscle Proteins/metabolism; MyoD Protein; Oligodeoxyribonucleotides/chemistry; Proto-Oncogene Proteins c-myc/metabolism; Structure-Activity Relationship; Transcription Factors;
Subjects: Molecules > Proteins > Transcription factors
Molecules > Molecular structure
Molecules > Genes > Oncogenes
Depositing User: Library Staff
Date Deposited: 01 Dec 2008 21:48
Last Modified: 21 May 2010 23:02

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