Transcription Factors and DNA Play Hide and Seek

Transcription factors (TFs) bind to specific DNA motifs to regulate the expression of target genes. To reach their binding sites, TFs diffuse in 3D and perform local motions such as 1D sliding, hopping, or intersegmental transfer. TF–DNA interactions depend on multiple parameters, such as the chromatin environment, TF partitioning into distinct subcellular regions, and cooperativity with other DNA-binding proteins. In this review, how current understanding of the search process has initially been shaped by prokaryotic studies is discussed, as well as what is known about the parameters regulating TF search efficiency in the context of the complex eukaryotic chromatin landscape. Transcription factors (TFs) search their specific sites through both 3D diffusion and local motions.TF search efficiency depends on TFs’ biochemical properties and local concentrations.Eukaryotic TFs vary strongly in their nonspecific DNA association and search efficiency.Progress in temporal and spatial resolution of single-molecule microscopy will be required to better describe the nanoscale movements of TFs on chromatin.