Systems Biophysics of Gene Expression

TL;DR

This paper reviews recent advances in systems biophysics that integrate molecular details into understanding gene regulation, highlighting how biophysical processes influence gene expression variability and response precision.

Contribution

It provides a comprehensive overview of how biophysical modeling elucidates gene regulation mechanisms across multiple scales, from molecular interactions to system-level behavior.

Findings

Understanding of promoter control over transcriptional noise

Insights into the role of protein-DNA interactions in gene regulation

Mechanistic explanations for variability and flexibility in gene expression

Abstract

Gene expression is a central process to any form of life. It involves multiple temporal and functional scales that extend from specific protein-DNA interactions to the coordinated regulation of multiple genes in response to intracellular and extracellular changes. This diversity in scales poses fundamental challenges among traditional approaches to fully understand even the simplest gene expression systems. Recent advances in computational systems biophysics have provided promising avenues to reliably integrate the molecular detail of biophysical process into the system behavior. Here, we review recent advances in the description of gene regulation as a system of biophysical processes that extend from specific protein-DNA interactions to the combinatorial assembly of nucleoprotein complexes. There is now basic mechanistic understanding on how promoters controlled by multiple, local and distal, DNA binding sites for transcription factors can actively control transcriptional noise, cell-to-cell variability, and other properties of gene regulation, including precision and flexibility of the transcriptional responses.