Mechanisms of DNA-binding specificity and functional gene regulation by transcription factors

Eukaryotic transcription factors up-regulate and down-regulate the expression of genes in a very controlled manner. The DNA-binding domains of these proteins have quite well established mechanisms for binding to DNA, but a surprisingly poor intrinsic ability to discriminate target and variant non-target DNA sequences. Here, we summarise established mechanisms of protein-DNA recognition, as specified by both macromolecules. We also review recent advances in the fields of genome binding, molecular dynamics and biomolecular interaction studies that bring us close to a full understanding of how eukaryotic transcription factors find and target DNA in vivo to form functional centres of gene regulation through networks of protein-protein and protein-DNA interactions.