Searching for the nik Operon: How a Ligand-Responsive Transcription Factor Hunts for Its DNA Binding Site

[Image: see text] Transcription factors regulate a wide variety of genes in the cell and play a crucial role in maintaining cellular homeostasis. A major unresolved issue is how transcription factors find their specific DNA binding sequence in the vast expanse of the cell and how they do so at rates that appear faster than the diffusion limit. Here, we relate an atomic-detail model that has been developed to describe the transcription factor NikR’s mechanism of DNA binding to the broader theories of how transcription factors find their binding sites on DNA. NikR is the nickel regulatory transcription factor for many bacteria, and NikR from Escherichia coli is one of the best studied ligand-mediated transcription factors. For the E. coli NikR protein, there is a wide variety of structural, biochemical, and computational studies that provide significant insight into the NikR−DNA binding mechanism. We find that the two models, the atomic-level model for E. coli NikR and the cellular model for transcription factors in general, are in agreement, and the details laid out by the NikR system may lend additional credence to the current models for transcription factors searching for DNA.