Quantitative modeling of transcription factor binding specificities using DNA shape
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- Tianyin Zhou
- Molecular and Computational Biology Program, Departments of Biological Sciences, Chemistry, Physics, and Computer Science, University of Southern California, Los Angeles, CA 90089;
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- Ning Shen
- Departments of bPharmacology and Cancer Biology and
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- Lin Yang
- Molecular and Computational Biology Program, Departments of Biological Sciences, Chemistry, Physics, and Computer Science, University of Southern California, Los Angeles, CA 90089;
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- Namiko Abe
- Departments of dBiochemistry and Molecular Biophysics and
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- John Horton
- Biostatistics and Bioinformatics and
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- Richard S. Mann
- Departments of dBiochemistry and Molecular Biophysics and
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- Harmen J. Bussemaker
- Systems Biology, Columbia University, New York, NY 10032; and
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- Raluca Gordân
- Biostatistics and Bioinformatics and
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- Remo Rohs
- Molecular and Computational Biology Program, Departments of Biological Sciences, Chemistry, Physics, and Computer Science, University of Southern California, Los Angeles, CA 90089;
抄録
<jats:title>Significance</jats:title> <jats:p>Genomes provide an abundance of putative binding sites for each transcription factor (TF). However, only small subsets of these potential targets are functional. TFs of the same protein family bind to target sites that are very similar but not identical. This distinction allows closely related TFs to regulate different genes and thus execute distinct functions. Because the nucleotide sequence of the core motif is often not sufficient for identifying a genomic target, we refined the description of TF binding sites by introducing a combination of DNA sequence and shape features, which consistently improved the modeling of in vitro TF−DNA binding specificities. Although additional factors affect TF binding in vivo, shape-augmented models reveal binding specificity mechanisms that are not apparent from sequence alone.</jats:p>
収録刊行物
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- Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences 112 (15), 4654-4659, 2015-03-09
Proceedings of the National Academy of Sciences
