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Nucleic Acids Res. 2014 Feb;42(4):2099-111. doi: 10.1093/nar/gkt1112. Epub 2013 Nov 16.

Protein-DNA binding: complexities and multi-protein codes.

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Department of Biology, Boston University, Boston, MA 02215, USA, Departments of Biostatistics and Bioinformatics, Computer Science, and Molecular Genetics and Microbiology, Institute for Genome Sciences and Policy, Duke University, Durham, NC 27708, USA.


Binding of proteins to particular DNA sites across the genome is a primary determinant of specificity in genome maintenance and gene regulation. DNA-binding specificity is encoded at multiple levels, from the detailed biophysical interactions between proteins and DNA, to the assembly of multi-protein complexes. At each level, variation in the mechanisms used to achieve specificity has led to difficulties in constructing and applying simple models of DNA binding. We review the complexities in protein-DNA binding found at multiple levels and discuss how they confound the idea of simple recognition codes. We discuss the impact of new high-throughput technologies for the characterization of protein-DNA binding, and how these technologies are uncovering new complexities in protein-DNA recognition. Finally, we review the concept of multi-protein recognition codes in which new DNA-binding specificities are achieved by the assembly of multi-protein complexes.

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