TY - JOUR
T1 - Eukaryotic gene regulation at equilibrium, or non?
AU - Zoller, Benjamin
AU - Gregor, Thomas
AU - Tkačik, Gašper
N1 - Funding Information:
This work was supported through the Center for the Physics of Biological Function (PHY– 1734030 ) and by National Institutes of Health Grants R01GM097275 and U01DK127429 (TG). GT acknowledges the support of the Austrian Science Fund grant FWF P28844 and the Human Frontiers Science Program.
Publisher Copyright:
© 2022 The Author(s)
PY - 2022/9
Y1 - 2022/9
N2 - Models of transcriptional regulation that assume equilibrium binding of transcription factors have been less successful at predicting gene expression from sequence in eukaryotes than in bacteria. This could be due to the non-equilibrium nature of eukaryotic regulation. Unfortunately, the space of possible non-equilibrium mechanisms is vast and predominantly uninteresting. The key question is therefore how this space can be navigated efficiently, to focus on mechanisms and models that are biologically relevant. In this review, we advocate for the normative role of theory—theory that prescribes rather than just describes—in providing such a focus. Theory should expand its remit beyond inferring mechanistic models from data, towards identifying non-equilibrium gene regulatory schemes that may have been evolutionarily selected, despite their energy consumption, because they are precise, reliable, fast, or otherwise outperform regulation at equilibrium. We illustrate our reasoning by toy examples for which we provide simulation code.
AB - Models of transcriptional regulation that assume equilibrium binding of transcription factors have been less successful at predicting gene expression from sequence in eukaryotes than in bacteria. This could be due to the non-equilibrium nature of eukaryotic regulation. Unfortunately, the space of possible non-equilibrium mechanisms is vast and predominantly uninteresting. The key question is therefore how this space can be navigated efficiently, to focus on mechanisms and models that are biologically relevant. In this review, we advocate for the normative role of theory—theory that prescribes rather than just describes—in providing such a focus. Theory should expand its remit beyond inferring mechanistic models from data, towards identifying non-equilibrium gene regulatory schemes that may have been evolutionarily selected, despite their energy consumption, because they are precise, reliable, fast, or otherwise outperform regulation at equilibrium. We illustrate our reasoning by toy examples for which we provide simulation code.
KW - Gene regulation
KW - Modeling
KW - Non-equilibrium regulation
KW - Optimization
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U2 - 10.1016/j.coisb.2022.100435
DO - 10.1016/j.coisb.2022.100435
M3 - Review article
C2 - 36590072
AN - SCOPUS:85142191139
SN - 2452-3100
VL - 31
JO - Current Opinion in Systems Biology
JF - Current Opinion in Systems Biology
M1 - 100435
ER -