Much of our knowledge of the rates of intracellular diffusion of regulatory transcription factor proteins (TFs) comes from live single-molecule tracking studies in the model organism Escherichia coli. These studies demonstrate that intracellular diffusion is extremely rapid, and that proteins are free to quickly homogenize throughout the cell. However, results from our lab indicate that the situation is in fact far more complex: the rate and extent of intracellular TF diffusion is highly dependent upon the degree of molecular crowding, and that E. coli can change the degree of intracellular molecular crowding and spatially redistribute TFs by altering its morphology and the condensation state of its DNA in response to growth conditions. I will discuss our latest findings, our current model to explain these results, how our observations can be reconciled with previous studies demonstrating rapid diffusion, and the possible consequences of these findings for genomic organization.
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