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Validity of quasi‑equilibrium statistical mechanical models for eukaryotic transcriptional regulation

Establish whether the quasi‑equilibrium Monod–Wyman–Changeux–style statistical mechanical framework, which treats regulatory occupancy as an equilibrium quantity determining transcriptional rates, accurately describes eukaryotic transcriptional regulation under physiological conditions.

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Background

The Monod–Wyman–Changeux (MWC) framework and related equilibrium statistical mechanical models are widely used to describe transcriptional regulation, assuming rates are proportional to occupancies computed at equilibrium.

While these methods offer tractable parameterizations for multi-factor regulation, their applicability to eukaryotic gene regulation—which involves dynamic, energy-consuming processes—has been questioned and requires direct validation or refutation.

References

There is a tradition of using such equilibrium arguments for transcriptional control as well, although the validity of this quasi--equilibrium view remains an open question.

Ambitions for theory in the physics of life (2401.15538 - Bialek, 28 Jan 2024) in Section Ingredients of a genetic network (MWC model for regulation)