Single gene analysis in yeast suggests nonequilibrium regulatory dynamics for transcription

• Published in: Nature communications 2024-07, Vol.15 (1), p.6226-9, Article 6226
• Main Authors: Shelansky, Robert, Abrahamsson, Sara, Brown, Christopher R., Doody, Michael, Lenstra, Tineke L., Larson, Daniel R., Boeger, Hinrich
• Format: Article
• Language: English
• Subjects: 147/28; 38/32; 45/41; 631/337/572; 631/57/2265; 96/35; 96/63; Adenosine Triphosphate - metabolism; Chromatin; Chromatin Assembly and Disassembly; Data processing; Equilibrium; Eukaryotes; Free energy; Gene expression; Gene Expression Regulation, Fungal; Humanities and Social Sciences; Information processing; Kinetics; multidisciplinary; Regulatory mechanisms (biology); Regulatory sequences; Reservoirs; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Science; Science (multidisciplinary); Stochastic processes; Stochasticity; Transcription activation; Transcription factors; Transcription Factors - genetics; Transcription Factors - metabolism; Transcription initiation; Transcription, Genetic; Yeast; Yeasts
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-50419-5

Fluctuations in the initiation rate of transcription, the first step in gene expression, ensue from the stochastic behavior of the molecular process that controls transcription. In steady state, the regulatory process is often assumed to operate reversibly, i.e., in equilibrium. However, reversibility imposes fundamental limits to information processing. For instance, the assumption of equilibrium is difficult to square with the precision with which the regulatory process executes its task in eukaryotes. Here we provide evidence — from microscopic analyses of the transcription dynamics at a single gene copy of yeast — that the regulatory process for transcription is cyclic and irreversible (out of equilibrium). The necessary coupling to reservoirs of free energy occurs via sequence-specific transcriptional activators and the recruitment, in part, of ATP-dependent chromatin remodelers. Our findings may help explain how eukaryotic cells reconcile the dual but opposing requirements for fast regulatory kinetics and high regulatory specificity. Here the authors show that the regulatory mechanism for transcription of the yeast PHO5 gene operates away from equilibrium, contrary to common assumption about transcriptional regulatory processes. This occurs through the activation domain of the Pho4 activator, which mediates coupling to reservoirs of free energy.