19 Oct 2007
Leonid Mirny
HST Program and Department of Physics
MIT
In the process of protein-DNA recognition, a transcription factor (TF) rapidly searches for its specific site on a long DNA molecule and then strongly binds to this site. I will discuss mechanisms that can provide both a fast search and high stability of the protein-DNA complex.
We revisit previously-proposed models of the TF search process and use experimental measurements to show that the search process is quite slow, unless there is a large copy number of the TF or co-localization of the transcription factor with its binding site. Through a bioinformatics study, we show that this biophysical constraint may shape the organization of prokaryotic genomes.
Next, I will use recent biochemical and genomics data to argue that eukaryotic TFs are deficient in their specificity. I will demonstrate that DNA chromatization can not only hamper the process of protein-DNA recognition, but can also provide a mechanism for faster search and more specific binding.