A role for ATP-dependent chromatin remodeling in the hierarchical cooperativity between noninteracting transcription factors

TL;DR

This paper explores how ATP-dependent chromatin remodeling influences the cooperative interactions between noninteracting transcription factors, revealing non-equilibrium mechanisms that regulate gene expression.

Contribution

It introduces a non-equilibrium framework for understanding chromatin remodeling's role in transcription factor cooperativity, challenging traditional equilibrium-based models.

Findings

Non-equilibrium chromatin remodeling facilitates transcription factor cooperation.

Breaking equilibrium avoids molecular trapping phenomena.

Mechanism explains promoter responsiveness to transcription factor combinations.

Abstract

Chromatin remodeling machineries are abundant and diverse in eukaryotic cells. They have been involved in a variety of situations such as histone exchange and DNA repair, but their importance in gene expression remains unclear. Although the influence of nucleosome position on the regulation of gene expression is generally envisioned under the quasi-equilibrium perspective, it is proposed that given the ATP-dependence of chromatin remodeling enzymes, certain mechanisms necessitate non-equilibrium treatments. Examination of the celebrated chromatin remodeling system of the mouse mammary tumor virus, in which the binding of transcription factors opens the way to other ones, reveals that breaking equilibrium offers a subtle mode of transcription factor cooperativity, avoids molecular trapping phenomena and allows to reconcile previously conflicting experimental data. This mechanism provides a control lever of promoter responsiveness to transcription factor combinations, challenging the classical view of the unilateral influence of pioneer on secondary transcription factors.