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

Matthew Slattery, Tianyin Zhou, Lin Yang, Ana Carolina Dantas Machado, Raluca Gordân, Remo Rohs

Research output: Contribution to journalReview articlepeer-review

248 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)381-399
Number of pages19
JournalTrends in Biochemical Sciences
Volume39
Issue number9
DOIs
StatePublished - Sep 2014

Bibliographical note

Funding 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.

Keywords

  • Chromatin
  • Cofactor
  • Cooperativity
  • DNA binding specificity models
  • High-throughput binding assays
  • Protein-DNA recognition

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