GR and HMGB1 interact only within chromatin and influence each other’s residence time

Most
nuclear proteins reside on a specific chromatin site only for seconds or less. The hit-and-run model of transcriptional control maintains that transcription complexes are assembled in a stochastic fashion from
freely diffusible proteins; this contrasts to models involving stepwise assembly of stable holo complexes.
However, the chances of forming a productive complex improve if the binding of one factor promotes
the binding of its interactors. We prove here that in living cells, the glucocorticoid receptor and HMGB1 interact only within chromatin and not in the nucleoplasm and decrease each other’s mobility.
Thus, the formation of a GR-HMGB1-chromatin complex
is more likely than one would expect from independent binding to chromatin of GR and HMGB1. Remarkably, this complex is potentially stable, and its
disassembly is effected by active, ATP-consuming processes.
We propose that kinetic cooperativity
among transcription factors in chromatin binding may be a common feature in transcription and DNA transactions.