Governing principles of transcriptional logic out of equilibrium

Biophys J. 2024 Mar 14:S0006-3495(24)00185-1. doi: 10.1016/j.bpj.2024.03.020. Online ahead of print.ABSTRACTTo survive, adapt, and develop, cells respond to external and internal stimuli, by tightly regulating transcription. Transcriptional regulation involves the combinatorial binding of a repertoire of transcription factors (TFs) to DNA, which often results in switch-like binary outputs, akin to Boolean logic gates. Recent experimental studies have demonstrated that in eukaryotes, transcription factor binding to DNA often involves energy expenditure, thereby driving the system out of equilibrium. The governing principles of transcriptional logic operations out of equilibrium remain unexplored. Here we employ a simple two-input, single-locus model of transcription that can accommodate both equilibrium and non-equilibrium mechanisms. Using this model, we find that non-equilibrium regimes can give rise to all the logic operations accessible in equilibrium. Strikingly, energy expenditure alters the regulatory function of the two transcription factors in a mutually exclusive manner. This allows for the emergence of new logic operations that are inaccessible in equilibrium. Overall, our results show that energy expenditure can expand the range of cellular decision-making without the need for more complex promoter architectures.PMID:38486450 | DOI:10.1016/j.bpj.2024.03.020

Source: Biophysical Journal - March 15, 2024 Category: Physics Authors: Smruti Dixit Teije C Middelkoop Sandeep Choubey Source Type: research