The needle and the haystack: single molecule tracking to probe the transcription factor search in eukaryotes

Biochem Soc Trans. 2021 Jun 30;49(3):1121-1132. doi: 10.1042/BST20200709.

Abstract

Transcription factors (TFs) regulate transcription of their target genes by identifying and binding to regulatory regions of the genome among billions of potential non-specific decoy sites, a task that is often presented as a 'needle in the haystack' challenge. The TF search process is now well understood in bacteria, but its characterization in eukaryotes needs to account for the complex organization of the nuclear environment. Here we review how live-cell single molecule tracking is starting to shed light on the TF search mechanism in the eukaryotic cell and we outline the future challenges to tackle in order to understand how nuclear organization modulates the TF search process in physiological and pathological conditions.

Keywords: search mechanism; single molecule; transcription factors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Binding Sites / genetics
  • Cell Nucleus / genetics
  • Cell Nucleus / metabolism
  • Eukaryota / genetics
  • Eukaryota / metabolism*
  • Gene Expression Regulation*
  • Genome / genetics*
  • Humans
  • Protein Binding
  • Regulatory Sequences, Nucleic Acid / genetics*
  • Single Molecule Imaging / methods*
  • Transcription Factors / metabolism*

Substances

  • Transcription Factors