{rfName}
A

Indexed in

License and Use

Icono OpenAccess

Citations

33

Altmetrics

Analysis of institutional authors

Miro-Bueno, Jesus M.Corresponding AuthorRodriguez-Paton, AlfonsoAuthor

Share

June 9, 2019
Publications
>
Article
Sí

A Simple Negative Interaction in the Positive Transcriptional Feedback of a Single Gene Is Sufficient to Produce Reliable Oscillations

Publicated to: Plos One. 6 (11): e27414- - 2011-11-10 6(11), DOI: 10.1371/journal.pone.0027414

Authors:

Miro-Bueno, Jesus M.; Rodriguez-Paton, Alfonso;
[+]

Affiliations

Univ Politecn Madrid, Dept Inteligencia Artificial, Fac Informat, Madrid, Spain - Author

Abstract

Negative and positive transcriptional feedback loops are present in natural and synthetic genetic oscillators. A single gene with negative transcriptional feedback needs a time delay and sufficiently strong nonlinearity in the transmission of the feedback signal in order to produce biochemical rhythms. A single gene with only positive transcriptional feedback does not produce oscillations. Here, we demonstrate that this single-gene network in conjunction with a simple negative interaction can also easily produce rhythms. We examine a model comprised of two well-differentiated parts. The first is a positive feedback created by a protein that binds to the promoter of its own gene and activates the transcription. The second is a negative interaction in which a repressor molecule prevents this protein from binding to its promoter. A stochastic study shows that the system is robust to noise. A deterministic study identifies that the dynamics of the oscillator are mainly driven by two types of biomolecules: the protein, and the complex formed by the repressor and this protein. The main conclusion of this paper is that a simple and usual negative interaction, such as degradation, sequestration or inhibition, acting on the positive transcriptional feedback of a single gene is a sufficient condition to produce reliable oscillations. One gene is enough and the positive transcriptional feedback signal does not need to activate a second repressor gene. This means that at the genetic level an explicit negative feedback loop is not necessary. The model needs neither cooperative binding reactions nor the formation of protein multimers. Therefore, our findings could help to clarify the design principles of cellular clocks and constitute a new efficient tool for engineering synthetic genetic oscillators.
[+]

Keywords

AlgorithmsCellular control processesComputer simulationExpressionFeedback, physiologicalGene expression regulationGene regulatory networksGoodwin modelLoopsMathematicsModels, geneticNetworksNeurospora circadian clockNoisePromoter regions, geneticProtein bindingProteinsRhythmsSimulationSoftwareStochastic processesTranscription, genetic

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Plos One due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2011, it was in position 12/85, thus managing to position itself as a Q1 (Primer Cuartil), in the category Biology.

Independientemente del impacto esperado determinado por el canal de difusión, es importante destacar el impacto real observado de la propia aportación.

Según las diferentes agencias de indexación, el número de citas acumuladas por esta publicación hasta la fecha 2025-12-19:

  • WoS: 11
  • Scopus: 13
  • Europe PMC: 8
[+]

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-12-19:

  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 36 (PlumX).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.
[+]

Leadership analysis of institutional authors

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: First Author (MIRO BUENO, JESUS MARIA) and Last Author (RODRIGUEZ-PATON ARADAS, ALFONSO VICENTE).

the author responsible for correspondence tasks has been MIRO BUENO, JESUS MARIA.

[+]

Awards linked to the item

This research has been partially funded by Spanish Ministry of Science and Innovation (MICINN) grant BES-2007-16220 and project TIN2009-14421, by the UPM and Madrid Regional Government and by research project BACTOCOM funded by European Commission under FP7, FET proactive program. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
[+]