Abstract
From the viewpoint of thermodynamics, the formation of DNA loops and the interaction between them, which are all non-equilibrium processes, result in the change of free energy, affecting gene expression and further cell-to-cell variability as observed experimentally. However, how these processes dissipate free energy remains largely unclear. Here, by analyzing a mechanic model that maps three fundamental topologies of two interacting DNA loops into a 4-state model of gene transcription, we first show that a longer DNA loop needs more mean free energy consumption. Then, independent of the type of interacting two DNA loops (nested, side-by-side or alternating), the promotion between them always consumes less mean free energy whereas the suppression dissipates more mean free energy. More interestingly, we find that in contrast to the mechanism of direct looping between promoter and enhancer, the facilitated-tracking mechanism dissipates less mean free energy but enhances the mean mRNA expression, justifying the facilitated-tracking hypothesis, a long-standing debate in biology. Based on minimal energy principle, we thus speculate that organisms would utilize the mechanisms of loop-loop promotion and facilitated tracking to survive in complex environments. Our studies provide insights into the understanding of gene expression regulation mechanism from the view of energy consumption.
Highlights
From the viewpoint of thermodynamics, the formation of DNA loops and the interaction between them, which are all non-equilibrium processes, result in the change of free energy, affecting gene expression and further cell-to-cell variability as observed experimentally
Apart from showing that a longer DNA loop needs more mean free energy consumption, we find that the promotion of two loops always reduces the mean free energy consumption whereas the suppression has the opposite effect, both independent of the topology of two DNA loops; in contrast to the mechanism of direct looping between regulatory elements, the facilitated-tracking mechanism dissipates less mean free energy and can enhance the mean mRNA expression, justifying the facilitated-tracking hypothesis in biology
Whether two DNA regulatory elements form a loop depends on the distance between them along the DNA line, and that this distance in turn can affect gene expression and further cell-to-cell variability[18,19]
Summary
From the viewpoint of thermodynamics, the formation of DNA loops and the interaction between them, which are all non-equilibrium processes, result in the change of free energy, affecting gene expression and further cell-to-cell variability as observed experimentally. They argued that the combination of loop assistance and loop interference can provide strong specificity in long-range interactions Another similar but important work is that Savitskaya, et al, experimentally observed[13] that when a pair of repressor (Su and Hw) found in the gypsy retrotransposon and their binding sites are in between the enhancer and the promoter, the gene expression level is not decreased but increased. Storage and retrieval of the genetic information in a cell are a dynamic process that requires the DNA to undergo structural rearrangements essential for transcriptional regulation in prokaryotic and eukaryotic cells[31], DNA looping and the interaction between DNA loops are two prominent examples of such a structural deformation This deformation belonging to energy-dependent chromatin remodeling necessarily dissipates energy. The minimal energy principle would provide a good angle of view for understanding the regulatory mechanism of the interaction of DNA loops, but because of the complexity of biological regulations, energy calculation is nontrivial and needs to develop new methods
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