Fundamentally different strategies for transcriptional regulation are revealed by information-theoretical analysis of binding motifs

TL;DR

This study uses information-theoretical analysis to reveal that prokaryotic and eukaryotic transcription factors employ fundamentally different strategies for gene regulation, with eukaryotes relying on clustering of binding sites due to widespread nonfunctional binding.

Contribution

It demonstrates distinct regulatory strategies in prokaryotes and eukaryotes based on analysis of 319 TF binding motifs, highlighting the role of site clustering in eukaryotic specificity.

Findings

Eukaryotic TFs show widespread nonfunctional binding.

Eukaryotes require clustering of binding sites for specificity.

Prokaryotic TFs use different targeting strategies.

Abstract

To regulate a particular gene, a transcription factor (TF) needs to bind a specific genome location. How is this genome address specified amid the presence of ~10^6-10^9 decoy sites? Our analysis of 319 known TF binding motifs clearly demonstrates that prokaryotes and eukaryotes use strikingly different strategies to target TFs to specific genome locations; eukaryotic TFs exhibit widespread nonfunctional binding and require clustering of sites in regulatory regions for specificity.