Researchers have captured images of individual proteins searching for their DNA-binding sites, and have quantified parts of this process.

Zhe Liu and his team at the Howard Hughes Medical Institute in Ashburn, Virginia, looked at transcription factors — proteins that bind to specific genes to regulate their activity — in individual, living mouse embryonic stem cells. The researchers used microscopes to track single molecules of Sox2 and Oct4, key stem-cell gene regulators. They found that the two molecules use trial and error to seek out their binding sites, by colliding with DNA, diffusing away and colliding again roughly 90 times before finding their targets. The process takes about 6 minutes and the factors remain bound to the target sites for about 12 to 14 seconds.

Sox2 collides and then slides along short stretches of DNA. Sox2 also binds before Oct4, helping it to find its home.

Cell 156, 1274–1285 (2014)