Hinrich Böger: Breaking Reversibility in Eukaryotic Gene Regulation: Enhancing Activator Specificity via Energy Coupling

Speaker:
Hinrich Böger (UC Santa Cruz)

Title:
Breaking Reversibility in Eukaryotic Gene Regulation: Enhancing Activator Specificity via Energy Coupling

Abstract:
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 ¾ obtained from single-molecule observations of a eukaryotic gene in yeast ¾ reveals a regulatory process far from equilibrium. We show that 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. This enhanced specificity can be accounted for by a simple kinetic proofreading model, in which free energy dissipation enables promoter discrimination beyond the limits imposed by equilibrium.

Lecture Series:
SysBio Lecture Series: AI for Systems Medicine