Control of gene expression by modulated self-assembly

TL;DR

This paper introduces a quantitative framework demonstrating how modulated self-assembly of transcription factors enhances gene regulation precision and flexibility, unifying diverse cellular signaling mechanisms.

Contribution

It provides the first general model linking self-assembly to gene expression control, explaining diverse regulatory behaviors in transcription factors like RXR.

Findings

Accurately reproduces classical gene expression data for RXR.

Identifies a functional regime with tunable precision and flexibility.

Shows self-assembly as a key regulator of gene expression dynamics.

Abstract

Numerous transcription factors self-assemble into different order oligomeric species in a way that is actively regulated by the cell. Until now, no general functional role has been identified for this widespread process. Here we capture the effects of modulated self-assembly in gene expression with a novel quantitative framework. We show that this mechanism provides precision and flexibility, two seemingly antagonistic properties, to the sensing of diverse cellular signals by systems that share common elements present in transcription factors like p53, NF-kappaB, STATs, Oct, and RXR. Applied to the nuclear hormone receptor RXR, this framework accurately reproduces a broad range of classical, previously unexplained, sets of gene expression data and corroborates the existence of a precise functional regime with flexible properties that can be controlled both at a genome-wide scale and at the individual promoter level.