Diversity and complexity in DNA recognition by transcription factors

Science. 2009 Jun 26;324(5935):1720-3. doi: 10.1126/science.1162327. Epub 2009 May 14.

Abstract

Sequence preferences of DNA binding proteins are a primary mechanism by which cells interpret the genome. Despite the central importance of these proteins in physiology, development, and evolution, comprehensive DNA binding specificities have been determined experimentally for only a few proteins. Here, we used microarrays containing all 10-base pair sequences to examine the binding specificities of 104 distinct mouse DNA binding proteins representing 22 structural classes. Our results reveal a complex landscape of binding, with virtually every protein analyzed possessing unique preferences. Roughly half of the proteins each recognized multiple distinctly different sequence motifs, challenging our molecular understanding of how proteins interact with their DNA binding sites. This complexity in DNA recognition may be important in gene regulation and in the evolution of transcriptional regulatory networks.

Publication types

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

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Binding Sites
  • DNA / chemistry
  • DNA / metabolism*
  • Electrophoretic Mobility Shift Assay
  • Gene Expression Regulation
  • Gene Regulatory Networks
  • Humans
  • Mice
  • Protein Array Analysis
  • Protein Binding
  • Protein Structure, Tertiary
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / metabolism
  • Transcription Factors / chemistry*
  • Transcription Factors / metabolism*

Substances

  • Recombinant Fusion Proteins
  • Transcription Factors
  • DNA