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A universal system for boosting gene expression in eukaryotic cell-lines

Author

Listed:
  • Inbal Vaknin

    (Technion)

  • Or Willinger

    (Technion)

  • Jonathan Mandl

    (Bar-Ilan University)

  • Hadar Heuberger

    (Ben-Gurion University of the Negev)

  • Dan Ben-Ami

    (Ben-Gurion University of the Negev)

  • Yi Zeng

    (Technion)

  • Sarah Goldberg

    (Technion)

  • Yaron Orenstein

    (Bar-Ilan University
    Bar-Ilan University)

  • Roee Amit

    (Technion
    Technion)

Abstract

We demonstrate a transcriptional regulatory design algorithm that can boost expression in yeast and mammalian cell lines. The system consists of a simplified transcriptional architecture composed of a minimal core promoter and a synthetic upstream regulatory region (sURS) composed of up to three motifs selected from a list of 41 motifs conserved in the eukaryotic lineage. The sURS system was first characterized using an oligo-library containing 189,990 variants. We validate the resultant expression model using a set of 43 unseen sURS designs. The validation sURS experiments indicate that a generic set of grammar rules for boosting and attenuation may exist in yeast cells. Finally, we demonstrate that this generic set of grammar rules functions similarly in mammalian CHO-K1 and HeLa cells. Consequently, our work provides a design algorithm for boosting the expression of promoters used for expressing industrially relevant proteins in yeast and mammalian cell lines.

Suggested Citation

  • Inbal Vaknin & Or Willinger & Jonathan Mandl & Hadar Heuberger & Dan Ben-Ami & Yi Zeng & Sarah Goldberg & Yaron Orenstein & Roee Amit, 2024. "A universal system for boosting gene expression in eukaryotic cell-lines," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-46573-5
    DOI: 10.1038/s41467-024-46573-5
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    References listed on IDEAS

    as
    1. Florian Wagner, 2015. "GO-PCA: An Unsupervised Method to Explore Gene Expression Data Using Prior Knowledge," PLOS ONE, Public Library of Science, vol. 10(11), pages 1-26, November.
    2. Heidi Redden & Hal S. Alper, 2015. "The development and characterization of synthetic minimal yeast promoters," Nature Communications, Nature, vol. 6(1), pages 1-9, November.
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