  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.
