دورية أكاديمية
The unreasonable effectiveness of equilibrium gene regulation through the cell cycle.
| العنوان: | The unreasonable effectiveness of equilibrium gene regulation through the cell cycle. |
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| المؤلفون: | Vilar JMG; Biofisika Institute (CSIC, UPV/EHU), University of the Basque Country (UPV/EHU), P.O. Box 644, 48080 Bilbao, Spain; IKERBASQUE, Basque Foundation for Science, 48011 Bilbao, Spain. Electronic address: vilar@ikerbasque.org., Saiz L; Department of Biomedical Engineering, University of California, 451 E. Health Sciences Drive, Davis, CA 95616, USA; Max Planck Institute for the Physics of Complex Systems, 01187 Dresden, Germany; Center for Systems Biology Dresden, 01307 Dresden, Germany. Electronic address: lsaiz@ucdavis.edu. |
| المصدر: | Cell systems [Cell Syst] 2024 Jul 17; Vol. 15 (7), pp. 639-648.e2. Date of Electronic Publication: 2024 Jul 08. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Cell Press Country of Publication: United States NLM ID: 101656080 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2405-4720 (Electronic) Linking ISSN: 24054712 NLM ISO Abbreviation: Cell Syst Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: [Cambridge, MA] : Cell Press, [2015]- |
| مواضيع طبية MeSH: | Cell Cycle*/genetics , DNA Replication*, Lac Operon ; Gene Expression Regulation ; Cyclic AMP Receptor Protein/metabolism ; Cyclic AMP Receptor Protein/genetics ; Transcription, Genetic ; Escherichia coli/genetics ; Escherichia coli/metabolism ; Kinetics |
| مستخلص: | Systems like the prototypical lac operon can reliably hold repression of transcription upon DNA replication across cell cycles with just 10 repressor molecules per cell and behave as if they were at equilibrium. The origin of this phenomenology is still an unresolved question. Here, we develop a general theory to analyze strong perturbations in quasi-equilibrium systems and use it to quantify the effects of DNA replication in gene regulation. We find a scaling law linking actual with predicted equilibrium transcription via a single kinetic parameter. We show that even the lac operon functions beyond the physical limits of naive regulation through compensatory mechanisms that suppress non-equilibrium effects. Synthetic systems without adjuvant activators, such as the cAMP receptor protein (CRP), lack this reliability. Our results provide a rationale for the function of CRP, beyond just being a tunable activator, as a mitigator of cell cycle perturbations. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2024 Elsevier Inc. All rights reserved.) |
| فهرسة مساهمة: | Keywords: DNA replication effects; gene regulation; non-equilibrium binding; systems biology; transcription |
| المشرفين على المادة: | 0 (Cyclic AMP Receptor Protein) |
| تواريخ الأحداث: | Date Created: 20240709 Date Completed: 20240718 Latest Revision: 20240719 |
| رمز التحديث: | 20240720 |
| DOI: | 10.1016/j.cels.2024.06.002 |
| PMID: | 38981487 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 2405-4720 |
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| DOI: | 10.1016/j.cels.2024.06.002 |