How Transcription Factors Depart Their Targets In Cells

Binding of transcription factor proteins to genes is known to initiate gene transcription to mRNA and subsequent translation to protein. But the influences that cause transcription factors to detach from their gene targets in living cells are not as well understood. In vitro studies have shown that higher levels of free transcription factors in solution are associated with faster transcription factor release or faster exchanges of one for another. Peng Chen and coworkers at Cornell University have now used single-molecule assays to study this release and exchange process in living cells (Nat. Commun. 2015, DOI: 10.1038/ncomms8445). The study shows that higher concentrations of transcription factors in cells, like higher levels in vitro, are associated with faster unbinding of transcription factors from DNA. The free transcription factors either kick out or replace incumbent ones on DNA targets in cells, Chen explains. The study also shows that as chromosomes condense and become more compact, transcription factors detach faster. “Transcription factor-DNA complexes are essentially under mechanical tension,” Chen says, “so changes in DNA tension from chromosome condensation help pop the regulators off DNA.”