Negative feedback confers mutational robustness in yeast transcription factor regulation.

Proceedings of the National Academy of Sciences of the United States of America
Charles M DenbyRachel B Brem

Abstract

Organismal fitness depends on the ability of gene networks to function robustly in the face of environmental and genetic perturbations. Understanding the mechanisms of this stability is one of the key aims of modern systems biology. Dissecting the basis of robustness to mutation has proven a particular challenge, with most experimental models relying on artificial DNA sequence variants engineered in the laboratory. In this work, we hypothesized that negative regulatory feedback could stabilize gene expression against the disruptions that arise from natural genetic variation. We screened yeast transcription factors for feedback and used the results to establish ROX1 (Repressor of hypOXia) as a model system for the study of feedback in circuit behaviors and its impact across genetically heterogeneous populations. Mutagenesis experiments revealed the mechanism of Rox1 as a direct transcriptional repressor at its own gene, enabling a regulatory program of rapid induction during environmental change that reached a plateau of moderate steady-state expression. Additionally, in a given environmental condition, Rox1 levels varied widely across genetically distinct strains; the ROX1 feedback loop regulated this variation, in that the ran...Continue Reading

References

Jul 22, 1998·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·D ThieffryJ Collado-Vides
Jul 22, 1998·Proceedings of the National Academy of Sciences of the United States of America·M Kirschner, J Gerhart
Dec 9, 1998·Nature·S L Rutherford, S Lindquist
Mar 10, 2001·Science·J L HartmanL Hartwell
Aug 30, 2001·Cell Stress & Chaperones·P M Schwartsburd
Jun 7, 2002·Nature·Christine QueitschSusan Lindquist
Nov 6, 2002·Journal of Molecular Biology·Nitzan RosenfeldUri Alon
Oct 10, 2003·Bioinformatics·Timothy L Bailey, William Stafford Noble
Oct 17, 2003·Nature·Won-Ki HuhErin K O'Shea
Jan 7, 2004·Nature Reviews. Genetics·Michael E WallMichael A Savageau
Sep 3, 2004·Nature·Christopher T HarbisonRichard A Young
Jan 22, 2005·Proceedings of the National Academy of Sciences of the United States of America·Rachel B Brem, Leonid Kruglyak
Feb 22, 2005·Nature Genetics·Ran KafriYitzhak Pilpel
May 13, 2005·Nature·Murat AcarAlexander van Oudenaarden
Mar 9, 2006·BMC Bioinformatics·Kenzie D MacIsaacErnest Fraenkel
Jun 2, 2006·Molecular Systems Biology·Ernesto AndrianantoandroRon Weiss
Aug 29, 2006·Nature Genetics·Stephen A RamseyJohn D Aitchison
Oct 19, 2006·Nature Reviews. Genetics·Matthew V Rockman, Leonid Kruglyak
May 19, 2007·Nature Reviews. Genetics·Uri Alon
Sep 20, 2007·Nature Reviews. Genetics·Michael Lynch
Jan 26, 2008·Science·Jerome T MettetalAlexander van Oudenaarden
Apr 3, 2008·Genome Research·Trey Ideker, Roded Sharan
Oct 18, 2008·Science·Onn Brandman, Tobias Meyer
Nov 7, 2008·PLoS Biology·Sasha F Levy, Mark L Siegal
Feb 13, 2009·Nature·Gianni LitiEdward J Louis
Apr 24, 2009·Nature·Sandra López-AvilésFrank Uhlmann
Apr 25, 2009·Science·Quincey A JustmanKevan M Shokat
Aug 28, 2009·Genes & Development·Nan WuMitchell A Lazar
Sep 1, 2009·Trends in Genetics : TIG·Joanna Masel, Mark L Siegal
Nov 6, 2009·Molecular Systems Biology·Orsolya KapuyBéla Novák
Feb 19, 2010·Nature·Arjun RajAlexander van Oudenaarden
May 13, 2010·Molecular Systems Biology·Michael SpringerMarc W Kirschner
Oct 12, 2010·Science·Murat AcarAlexander van Oudenaarden
Feb 18, 2011·Genome Research·Lesley T Macneil, Albertha J M Walhout
Jun 3, 2011·Proceedings of the National Academy of Sciences of the United States of America·Malte PaulsenChristof Niehrs
Jun 18, 2011·Science·Hao A DuongCharles J Weitz

❮ Previous
Next ❯

Citations

Sep 4, 2012·Antioxidants & Redox Signaling·Myriam BourensAntoni Barrientos
Apr 30, 2013·BMC Evolutionary Biology·Watal M IwasakiMasakado Kawata
Jan 7, 2014·PLoS Computational Biology·Guillem CasanovasStefan Legewie
Mar 22, 2014·Molecular Biology of the Cell·Meru J SadhuJasper Rine
Jun 3, 2015·Annual Review of Ecology, Evolution, and Systematics·Mark L Siegal, Jun-Yi Leu
Sep 26, 2012·Cellular and Molecular Life Sciences : CMLS·Nils Blüthgen, Stefan Legewie
May 21, 2013·Cell Biology International·Vasily V GrinevSergey V Gloushen
Nov 14, 2013·Evolution; International Journal of Organic Evolution·Tyler D Hether, Paul A Hohenlohe
Aug 22, 2015·Annals of Botany·Lamia Mestek Boukhibar, Michalis Barkoulas
Jun 10, 2014·Cell Reports·David C MarcianoOlivier Lichtarge
Nov 6, 2014·Molecular Biology and Evolution·Claudia BankDaniel N A Bolon
Apr 13, 2012·PloS One·Long YanHongli Wang
Nov 13, 2015·PLoS Genetics·Frédéric FyonThomas Lenormand
Jan 5, 2012·PLoS Computational Biology·Ralf SteuerMarkus Kollmann
Jan 31, 2015·Molecular Systems Biology·Daniel M BaderJulien Gagneur
Oct 4, 2017·Theoretical Biology & Medical Modelling·Youcef Derbal
May 20, 2016·Genetics·Justin M FearLauren M McIntyre
Jul 9, 2016·Physical Review Letters·David C MarcianoOlivier Lichtarge
Feb 13, 2021·NAR Genomics and Bioinformatics·Komaki InoueKeiichi Mochida
Apr 5, 2014·ACS Synthetic Biology·Elisa FrancoRichard M Murray
Apr 24, 2018·Trends in Genetics : TIG·Sarah A Signor, Sergey V Nuzhdin

❮ 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.

© 2022 Meta ULC. All rights reserved