Transcription factors (TFs) influence cell fate by interpreting the regulatory DNA within a genome. TFs recognize DNA in a specific manner; the mechanisms underlying this specificity have been identified for many TFs based on 3D structures of protein-DNA complexes. More recently, structural views have been complemented with data from high-throughput in vitro and in vivo explorations of the DNA-binding preferences of many TFs. Together, these approaches have greatly expanded our understanding of TF-DNA interactions. However, the mechanisms by which TFs select in vivo binding sites and alter gene expression remain unclear. Recent work has highlighted the many variables that influence TF-DNA binding, while demonstrating that a biophysical understanding of these many factors will be central to understanding TF function.
Bibliographical noteFunding Information:
The authors thank the reviewers and the editor for their very constructive comments and suggestions. This work was supported by the National Institutes of Health (grants R01GM106056, U01GM103804 and in part R01HG003008 to R.R.). Charges associated with open-access publishing of this article are defrayed through the National Science Foundation (grant MCB-1413539 to R.R.). R.G. and R.R. are Alfred P. Sloan Research Fellows.
- DNA binding specificity models
- High-throughput binding assays
- Protein-DNA recognition