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Gene regulation

Regulatory promoter architectures in the hands of thermodynamic modelling

Nature Reviews Genetics volume 24, page 349 (2023)Cite this article

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As stated by Jacob and Monod, the genome encodes a coordinated programme of protein synthesis and the means of controlling its execution. This statement is the basis for the hypothesis of predicting the protein landscape given the state of regulatory elements. Genomic-based technologies are quickly enriching our knowledge of the building blocks that constitute the regulatory modules formed by specific combinations of transcription factors (TFs) governing gene expression. The advance is such that detailed characterizations of regulated promoters are emerging for different cell types in higher organisms, eventually at the single-cell level, and we are beginning to see complete repertoires of TF binding sites for bacterial genomes.

In two seminal papers, Rob Phillips and colleagues described the conceptual framework (the ‘models’ paper) based on a statistical thermodynamics approach to quantitatively model regulated activity in promoters subject to regulation by multiple TFs (the ‘applications’ paper). The application of this formalism to molecular biology started with the modelling of the lambda repressor by Shea and Ackers in the 1980s.

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  1. Centro de Ciencias Genómicas, Universidad Nacional Autónoma de México, Morelos, Mexico

    Julio Collado-Vides

  2. Department of Biomedical Engineering, Boston University, Boston, MA, USA

    Julio Collado-Vides

  3. Center for Genomic Regulation (CRG), Universitat Pompeu Fabra, Barcelona, Spain

    Julio Collado-Vides

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  1. Julio Collado-Vides
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Correspondence to Julio Collado-Vides.

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Collado-Vides, J. Regulatory promoter architectures in the hands of thermodynamic modelling. Nat Rev Genet 24, 349 (2023). https://doi.org/10.1038/s41576-023-00578-w

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