Regulation of Yeast-to-Hyphae Transition in Yarrowia lipolytica

Research output: Contribution to journalJournal article – Annual report year: 2019Researchpeer-review

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  • Author: Pomraning, Kyle R.

    Pacific Northwest National Laboratory, United States

  • Author: Bredeweg, Erin L.

    Pacific Northwest National Laboratory, United States

  • Author: Kerkhoven, Eduard J.

    Chalmers University of Technology, Sweden

  • Author: Barry, Kerrie

    Joint Genome Institute, United States

  • Author: Haridas, Sajeet

    Joint Genome Institute, United States

  • Author: Hundley, Hope

    Joint Genome Institute, United States

  • Author: LaButti, Kurt

    Joint Genome Institute, United States

  • Author: Lipzen, Anna

    Joint Genome Institute, United States

  • Author: Yan, Mi

    Joint Genome Institute, United States

  • Author: Magnuson, Jon K.

    Lawrence Berkeley National Laboratory, United States

  • Author: Simmons, Blake A.

    Lawrence Berkeley National Laboratory, United States

  • Author: Grigoriev, Igor V.

    Joint Genome Institute, United States

  • Author: Nielsen, Jens

    Yeast Cell Factories, Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Kemitorvet, 2800, Kgs. Lyngby, Denmark

  • Author: Baker, Scott E.

    Pacific Northwest National Laboratory, United States

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The yeast Yarrowia lipolytica undergoes a morphological transition from yeast-to-hyphal growth in response to environmental conditions. A forward genetic screen was used to identify mutants that reliably remain in the yeast phase, which were then assessed by whole-genome sequencing. All the smooth mutants identified, so named because of their colony morphology, exhibit independent loss of DNA at a repetitive locus made up of interspersed ribosomal DNA and short 10- to 40-mer telomere-like repeats. The loss of repetitive DNA is associated with downregulation of genes with stress response elements (5'-CCCCT-3') and upregulation of genes with cell cycle box (5'-ACGCG-3') motifs in their promoter region. The stress response element is bound by the transcription factor Msn2p in Saccharomyces cerevisiae. We confirmed that the Y. lipolytica msn2 (Ylmsn2) ortholog is required for hyphal growth and found that overexpression of Ylmsn2 enables hyphal growth in smooth strains. The cell cycle box is bound by the Mbp1p/Swi6p complex in S. cerevisiae to regulate G1-to-S phase progression. We found that overexpression of either the Ylmbp1 or Ylswi6 homologs decreased hyphal growth and that deletion of either Ylmbp1 or Ylswi6 promotes hyphal growth in smooth strains. A second forward genetic screen for reversion to hyphal growth was performed with the smooth-33 mutant to identify additional genetic factors regulating hyphal growth in Y. lipolytica. Thirteen of the mutants sequenced from this screen had coding mutations in five kinases, including the histidine kinases Ylchk1 and Ylnik1 and kinases of the high-osmolarity glycerol response (HOG) mitogen-activated protein (MAP) kinase cascade Ylssk2, Ylpbs2, and Ylhog1. Together, these results demonstrate that Y. lipolytica transitions to hyphal growth in response to stress through multiple signaling pathways. IMPORTANCE: Many yeasts undergo a morphological transition from yeast-to-hyphal growth in response to environmental conditions. We used forward and reverse genetic techniques to identify genes regulating this transition in Yarrowia lipolytica. We confirmed that the transcription factor Ylmsn2 is required for the transition to hyphal growth and found that signaling by the histidine kinases Ylchk1 and Ylnik1 as well as the MAP kinases of the HOG pathway (Ylssk2, Ylpbs2, and Ylhog1) regulates the transition to hyphal growth. These results suggest that Y. lipolytica transitions to hyphal growth in response to stress through multiple kinase pathways. Intriguingly, we found that a repetitive portion of the genome containing telomere-like and rDNA repeats may be involved in the transition to hyphal growth, suggesting a link between this region and the general stress response.
Original languageEnglish
Article numbere00541-18
JournalmSphere
Volume3
Issue number6
Number of pages18
ISSN1535-9786
DOIs
Publication statusPublished - 2018
CitationsWeb of Science® Times Cited: No match on DOI

    Research areas

  • Yarrowia, Dimorphic, Genomics, Molecular genetics, Morphology, Signaling

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