A primer on thermodynamic-based models for deciphering transcriptional regulatory logic

•We provide a simple derivation for thermodynamic-based models of gene regulation.•We discuss the experimental data and analysis required for use in these models.•We describe common approaches used to analyze and implement these models.•We highlight the challenges of quantitative modeling of transcriptional regulation.•We discuss ways in which these challenges can be addressed in future studies.

A rigorous analysis of transcriptional regulation at the DNA level is crucial to the understanding of many biological systems. Mathematical modeling has offered researchers a new approach to understanding this central process. In particular, thermodynamic-based modeling represents the most biophysically informed approach aimed at connecting DNA level regulatory sequences to the expression of specific genes. The goal of this review is to give biologists a thorough description of the steps involved in building, analyzing, and implementing a thermodynamic-based model of transcriptional regulation. The data requirements for this modeling approach are described, the derivation for a specific regulatory region is shown, and the challenges and future directions for the quantitative modeling of gene regulation are discussed.