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.