Role of DNA binding sites and slow unbinding kinetics in titration-based oscillators

Physical Review. E, Statistical, Nonlinear, and Soft Matter Physics
Sargis Karapetyan, Nicolas E Buchler

Abstract

Genetic oscillators, such as circadian clocks, are constantly perturbed by molecular noise arising from the small number of molecules involved in gene regulation. One of the strongest sources of stochasticity is the binary noise that arises from the binding of a regulatory protein to a promoter in the chromosomal DNA. In this study, we focus on two minimal oscillators based on activator titration and repressor titration to understand the key parameters that are important for oscillations and for overcoming binary noise. We show that the rate of unbinding from the DNA, despite traditionally being considered a fast parameter, needs to be slow to broaden the space of oscillatory solutions. The addition of multiple, independent DNA binding sites further expands the oscillatory parameter space for the repressor-titration oscillator and lengthens the period of both oscillators. This effect is a combination of increased effective delay of the unbinding kinetics due to multiple binding sites and increased promoter ultrasensitivity that is specific for repression. We then use stochastic simulation to show that multiple binding sites increase the coherence of oscillations by mitigating the binary noise. Slow values of DNA unbinding rate ...Continue Reading

References

Feb 5, 2000·Nature·N Barkai, S Leibler
Feb 5, 2000·Nature·M B Elowitz, S Leibler
Jan 17, 2002·Proceedings of the National Academy of Sciences of the United States of America·Didier GonzeAlbert Goldbeter
Apr 25, 2002·Proceedings of the National Academy of Sciences of the United States of America·José M G VilarStanislas Leibler
Oct 17, 2003·Nature·Sina GhaemmaghamiJonathan S Weissman
Mar 11, 2004·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Motoki KyoMasayuki Yamamoto
Jan 1, 2005·Proceedings of the National Academy of Sciences of the United States of America·Daniel B Forger, Charles S Peskin
Mar 31, 2005·Current Opinion in Genetics & Development·Lacramioara BintuRob Phillips
Oct 26, 2005·Physical Review. E, Statistical, Nonlinear, and Soft Matter Physics·Paul François, Vincent Hakim
Dec 20, 2005·Cell·Ido GoldingEdward C Cox
Dec 20, 2005·Proceedings of the National Academy of Sciences of the United States of America·Aleksandra M WalczakPeter G Wolynes
Dec 31, 2005·Physical Review. E, Statistical, Nonlinear, and Soft Matter Physics·J E M HornosP G Wolynes
Jul 11, 2006·Chaos·Didier Gonze, Albert Goldbeter
Jul 11, 2006·Proceedings of the National Academy of Sciences of the United States of America·Sandeep KrishnaKim Sneppen
Aug 19, 2006·Proceedings of the National Academy of Sciences of the United States of America·Archana BelleErin K O'Shea
Oct 13, 2006·Bioinformatics·Stefan HoopsUrsula Kummer
Aug 2, 2007·Molecular Systems Biology·Wilson W WongJames C Liao
Oct 22, 2008·Journal of Molecular Biology·Nicolas E Buchler, Matthieu Louis
Oct 31, 2008·Nature·Jesse StrickerJeff Hasty
Oct 31, 2008·Nature Reviews. Molecular Cell Biology·Béla Novák, John J Tyson
May 21, 2009·Molecular Systems Biology·Nicolas E Buchler, Frederick R Cross
Feb 18, 2010·Genes & Development·Jerome S MenetMichael Rosbash
Jan 6, 2011·Molecular Systems Biology·Christian MillerPatrick Cramer
Sep 3, 2011·Science·Octavio Mondragón-PalominoJeff Hasty
Sep 27, 2012·Proceedings of the National Academy of Sciences of the United States of America·Marcel GeertzSebastian J Maerkl
Dec 6, 2012·Molecular Systems Biology·Jae Kyoung Kim, Daniel B Forger
Dec 12, 2012·Physical Review. E, Statistical, Nonlinear, and Soft Matter Physics·Anat BurgerPeter G Wolynes
Dec 1, 2002·Journal of Biological Physics·D GonzeA Goldbeter
Feb 5, 2013·Nature Methods·Pablo Perez-PineraCharles A Gersbach
Jul 16, 2013·Physical Review. E, Statistical, Nonlinear, and Soft Matter Physics·Darka LabavićHildegard Meyer-Ortmanns
Oct 31, 2013·Molecular Systems Biology·Leeat KerenEran Segal
Jan 29, 2014·Proceedings of the National Academy of Sciences of the United States of America·Davit A Potoyan, Peter G Wolynes

❮ Previous
Next ❯

Citations

Jan 19, 2018·Journal of the Royal Society, Interface·Zhipeng WangPeter G Wolynes
Feb 2, 2018·Journal of the Royal Society, Interface·Yen Ting Lin, Nicolas E Buchler
Sep 30, 2016·Journal of the Royal Society, Interface·Zhipeng WangPeter G Wolynes
Apr 18, 2017·PLoS Computational Biology·Dipjyoti DasSandeep Choubey
Nov 15, 2021·Biophysical Journal·Supravat Dey, Abhyudai Singh

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

Advances in Experimental Medicine and Biology
Jacques Rougemont, Felix Naef
PLoS Computational Biology
Raúl Guantes, Juan F Poyatos
© 2022 Meta ULC. All rights reserved