Roles of intrinsically disordered regions in transcription factor search

Transcription Factors (TFs) are proteins that regulate gene expression. The regulation mechanism is via the binding of a TF to a specific part of the gene associated with it, the TF's target. For the regulation to be effective, the TF has to be able to bind to the correct target and it should do so fast enough to allow the cell an appropriate reaction time to, e.g., the discovery or food or the detection of toxins. At the same time, the search process is limited to diffusive (slow) motion and to an environment saturated with ``false" targets, other parts of the DNA with similar sequences. In eukaryotic cells many TFs have an Intrinsically Disordered Region (IDR), --a long polymeric ``tail" constructed of hundreds of amino acids. The IDR of certain TFs were shown to take a key part in the search process and in this letter we develop a model that attempts to explain its contribution. We show that the IDR enables high affinity of the TF for its corresponding target and that the manner in which it does so could also shorten the search time