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

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  • Dirk Benzinger

    (ETH–Zürich)

  • Mustafa Khammash

    (ETH–Zürich)

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.

Suggested Citation

  • Dirk Benzinger & Mustafa Khammash, 2018. "Pulsatile inputs achieve tunable attenuation of gene expression variability and graded multi-gene regulation," Nature Communications, Nature, vol. 9(1), pages 1-10, December.
  • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05882-2
    DOI: 10.1038/s41467-018-05882-2
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    Cited by:

    1. François Bertaux & Sebastián Sosa-Carrillo & Viktoriia Gross & Achille Fraisse & Chetan Aditya & Mariela Furstenheim & Gregory Batt, 2022. "Enhancing bioreactor arrays for automated measurements and reactive control with ReacSight," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    2. Karl P. Gerhardt & Satyajit D. Rao & Evan J. Olson & Oleg A. Igoshin & Jeffrey J. Tabor, 2021. "Independent control of mean and noise by convolution of gene expression distributions," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    3. Vojislav Gligorovski & Ahmad Sadeghi & Sahand Jamal Rahi, 2023. "Multidimensional characterization of inducible promoters and a highly light-sensitive LOV-transcription factor," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    4. Ankit Gupta & Mustafa Khammash, 2022. "Frequency spectra and the color of cellular noise," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    5. Sebastián Sosa-Carrillo & Henri Galez & Sara Napolitano & François Bertaux & Gregory Batt, 2023. "Maximizing protein production by keeping cells at optimal secretory stress levels using real-time control approaches," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    6. Gita Naseri, 2023. "A roadmap to establish a comprehensive platform for sustainable manufacturing of natural products in yeast," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    7. Matthias Bec & Sylvain Pouzet & Céline Cordier & Simon Barral & Vittore Scolari & Benoit Sorre & Alvaro Banderas & Pascal Hersen, 2024. "Optogenetic spatial patterning of cooperation in yeast populations," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    8. Zachary R. Fox & Steven Fletcher & Achille Fraisse & Chetan Aditya & Sebastián Sosa-Carrillo & Julienne Petit & Sébastien Gilles & François Bertaux & Jakob Ruess & Gregory Batt, 2022. "Enabling reactive microscopy with MicroMator," Nature Communications, Nature, vol. 13(1), pages 1-8, December.
    9. Lucas Henrion & Juan Andres Martinez & Vincent Vandenbroucke & Mathéo Delvenne & Samuel Telek & Andrew Zicler & Alexander Grünberger & Frank Delvigne, 2023. "Fitness cost associated with cell phenotypic switching drives population diversification dynamics and controllability," Nature Communications, Nature, vol. 14(1), pages 1-13, December.

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