Genomic DNA consistently undergoes structural changes that are imposed by the cellular DNA packaging, and by fundamental processes such as replication, DNA repair, and transcription. Similar deformations have been seen in vitro in many protein-DNA complexes, including those of TFs and repair enzymes. However, the effect of these structural changes on DNA binding affinities was measured only for a limited number of proteins with a limited number of DNA sequences. Therefore, we currently do not understand nor can we predict the impact of such changes on DNA biochemistry in the genome.
We are developing and using novel high-throughput assays to study and characterize the impact of these genomic forces on the fundamental interactions between protein and DNA within the cell.