Millisecond exposure (left) captures single-molecule movement that otherwise appears as a blur (right).

XIE/ELSEVIER

Structural analysis, biochemistry, and theoretical models have built a picture of how individual transcription factors find, bind, and regulate their target genes. Now, for the first time, Johan Elf, Gene-Wei Li, and Sunney Xie (Harvard University, Cambridge, MA) provide moving pictures of this process in living cells.

The lac operon of Escherichia coli has been one of the most well-studied model systems of transcriptional regulation. When a lac repressor protein binds its operator sequence upstream of the operon, transcription is repressed. Upon binding of lactose metabolites (or analogues thereof, such as IPTG), the repressor dissociates from the operator, which enables transcription. Previous studies measured the kinetics of lac repressor binding and dissociation indirectly by analyzing the accumulation of gene products.

To follow directly the kinetics of individual lac repressors, the team...

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