Hinrich Boeger: Nucleosomal Proofreading of Activator Identity

The bacterial paradigm of transcriptional regulation assumes that fluctuations in transcriptional activity arise from regulatory processes in equilibrium.  In contrast, our analysis of stochastic transcription trajectories -- obtained from single-molecule observations of a eukaryotic gene in yeast -- reveals a regulatory process far from equilibrium.

The required coupling to free energy reservoirs is mediated by the activation domain of a transcription factor which recognizes promoter elements with a specificity exceeding that predicted by equilibrium thermodynamics.  A simple kinetic proofreading model explains this enhanced specificity, where free energy dissipation enables promoter discrimination beyond the limits imposed by equilibrium.