Absence of a simple code: how transcription factors read the genome

Trends Biochem Sci. 2014 Sep;39(9):381-99. doi: 10.1016/j.tibs.2014.07.002. Epub 2014 Aug 14.


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.

Keywords: DNA binding specificity models; chromatin; cofactor; cooperativity; high-throughput binding assays; protein-DNA recognition.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Binding Sites
  • Biophysical Phenomena / genetics*
  • Computational Biology
  • DNA / genetics*
  • DNA / metabolism
  • Genome / genetics*
  • Humans
  • Protein Binding
  • Transcription Factors / metabolism*


  • Transcription Factors
  • DNA