Pulsatile inputs achieve tunable attenuation of gene expression variability and graded multi-gene regulation

Nature Communications
Dirk Benzinger, Mustafa Khammash

Abstract

Many natural transcription factors are regulated in a pulsatile fashion, but it remains unknown whether synthetic gene expression systems can benefit from such dynamic regulation. Here we find, using a fast-acting, optogenetic transcription factor in Saccharomyces cerevisiae, that dynamic pulsatile signals reduce cell-to-cell variability in gene expression. We then show that by encoding such signals into a single input, expression mean and variability can be independently tuned. Further, we construct a light-responsive promoter library and demonstrate how pulsatile signaling also enables graded multi-gene regulation at fixed expression ratios, despite differences in promoter dose-response characteristics. Pulsatile regulation can thus lead to beneficial functional behaviors in synthetic biological systems, which previously required laborious optimization of genetic parts or the construction of synthetic gene networks.

References

Oct 6, 1988·Nature·I SadowskiM Ptashne
Jun 13, 2000·Nature·A Becskei, L Serrano
Jun 2, 2001·The Journal of Biological Chemistry·O GriesbeckR Y Tsien
Jun 21, 2002·Methods in Enzymology·R Daniel Gietz, Robin A Woods
Aug 17, 2002·Science·Michael B ElowitzPeter S Swain
Sep 10, 2002·Nature Biotechnology·Sae Shimizu-SatoPeter H Quail
Apr 11, 2003·Nature·William J BlakeJ J Collins
May 29, 2004·Science·Jonathan M Raser, Erin K O'Shea
Mar 26, 2005·Science·Juan M Pedraza, Alexander van Oudenaarden
Aug 27, 2005·Proceedings of the National Academy of Sciences of the United States of America·Hal AlperGregory Stephanopoulos
Dec 24, 2005·Nature·Dmitri VolfsonJeff Hasty
Dec 26, 2006·Molecular Cell·William J BlakeJames J Collins
May 6, 2008·Proceedings of the National Academy of Sciences of the United States of America·Viktor M BoerDavid Botstein
Sep 6, 2008·Microbiology and Molecular Biology Reviews : MMBR·Elke Nevoigt
Sep 23, 2008·Nature Methods·Arjun RajSanjay Tyagi
Oct 30, 2008·Cell·Arjun Raj, Alexander van Oudenaarden
Jan 16, 2009·The Biochemical Journal·Dmitry ShcherboDmitriy M Chudakov
Mar 13, 2009·Proceedings of the National Academy of Sciences of the United States of America·Dmitry NevozhayGábor Balázsi
Apr 11, 2009·BMC Bioinformatics·Florian HahneRobert Gentleman
Mar 10, 2010·Nucleic Acids Research·Kevin F MurphyJames J Collins
Nov 3, 2010·Nature Methods·Matthew J KennedyChandra L Tucker
Apr 5, 2011·Journal of Physics. Condensed Matter : an Institute of Physics Journal·Gašper Tkačik, Aleksandra M Walczak
Apr 3, 2012·Physical Review Letters·Filipe TostevinPieter Rein ten Wolde
Jun 30, 2012·Nature Methods·Fabrice de ChaumontJean-Christophe Olivo-Marin
Dec 25, 2012·Nucleic Acids Research·Jing LiangHuimin Zhao
Aug 3, 2013·ACS Synthetic Biology·Jordan AngDavid R McMillen
Aug 10, 2013·Journal of Molecular Biology·Eric A DavidsonTravis S Bayer
Sep 10, 2013·Nature Chemical Biology·Mohammad Fallahi-SichaniPeter K Sorger
Dec 7, 2013·Science·Joe H LevineMichael B Elowitz
Jan 15, 2014·Nature Methods·Christoph ZechnerHeinz Koeppl
Jan 15, 2014·Nature Chemical Biology·Laura B Motta-MenaKevin H Gardner
Dec 3, 2014·Trends in Biotechnology·Frank DelvigneSøren J Sørensen
Feb 11, 2015·Nature Chemical Biology·Lauren R Polstein, Charles A Gersbach
Jul 4, 2015·Comparative Cytogenetics·Prabhu Shankar LakshmananLudmila Khrustaleva
Aug 19, 2015·Cell Reports·Anders S Hansen, Erin K O'Shea
Oct 19, 2016·Current Opinion in Microbiology·Olivier BorkowskiTom Ellis

❮ Previous
Next ❯

Citations

Apr 4, 2019·Journal of the Royal Society, Interface·Zhixing Cao, Ramon Grima
Jul 4, 2019·Nucleic Acids Research·Michael Tyler Guinn, Gábor Balázsi
Dec 4, 2019·Biotechnology and Bioengineering·Jidapas My An-AdirekkunMegan N McClean
Jan 13, 2019·BMC Systems Biology·Lili WuQi Ouyang
Dec 6, 2019·Biochemical Society Transactions·Asli Azizoglu, Jörg Stelling
Mar 15, 2020·Nature Communications·Melinda Liu PerkinsMustafa Khammash
Oct 30, 2020·Yeast·David FigueroaFrancisco Salinas
Jan 14, 2021·Nature Communications·Alain R BonnyHana El-Samad
May 19, 2020·MethodsX·Alexander LetourneauMegan N McClean
Oct 17, 2020·The New Phytologist·John M Christie, Matias D Zurbriggen
Apr 28, 2021·Nature Chemical Biology·Edoardo RomanoBarbara Di Ventura
Dec 24, 2019·Journal of Agricultural and Food Chemistry·Xixian ChenNicholas D Lindley
Mar 6, 2019·ACS Synthetic Biology·Jackson O'Brien, Arvind Murugan
Sep 2, 2021·Cell Systems·Jessica B LeeAlbert J Keung
Oct 7, 2021·Nature Communications·Chetan AdityaJakob Ruess
Jan 8, 2022·ACS Synthetic Biology·Zhiqian WangHoujin Zhang
Oct 8, 2020··Megan N. McCleanBhuvana Krishnaswamy

❮ Previous
Next ❯

Methods Mentioned

BETA
flow cytometry
transfections
restriction-ligation
PCRs
PCR
smFISH

Software Mentioned

R
PWM
flowCore
CVODE package
Matlab scripts
custom

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.