DNA looping in gene regulation: from the assembly of macromolecular complexes to the control of transcriptional noise

The formation of DNA loops by proteins and protein complexes that bind at distal DNA sites plays a central role in many cellular processes, such as transcription, recombination, and replication. Here we review the basic thermodynamic concepts underlying the assembly of macromolecular complexes on looped DNA and the effects that this process has in the properties of gene regulation. Beyond the traditional view of DNA looping as a mechanism to increase the affinity of regulatory molecules for their cognate sites, recent developments indicate that DNA looping can also lead to the suppression of cell-to-cell variability, the control of transcriptional noise, and the activation of cooperative interactions on demand.