Regulation of yeast-to-hyphae transition in Yarrowia lipolytica
Journal article, 2018

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.

Dimorphic

Molecular genetics

Genomics

Morphology

Yarrowia

Signaling

Author

Kyle R. Pomraning

Pacific Northwest National Laboratory

Erin L. Bredeweg

Pacific Northwest National Laboratory

Eduard Kerkhoven

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Kerrie Barry

DOE Joint Genome Institute

Sajeet Haridas

DOE Joint Genome Institute

Hope Hundley

DOE Joint Genome Institute

Kurt LaButti

DOE Joint Genome Institute

Anna Lipzen

DOE Joint Genome Institute

Mi Yan

DOE Joint Genome Institute

J. K. Magnuson

Pacific Northwest National Laboratory

Lawrence Berkeley National Laboratory

Blake A. Simmons

Lawrence Berkeley National Laboratory

I. V. Grigoriev

DOE Joint Genome Institute

Jens B Nielsen

Technical University of Denmark (DTU)

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

S. E. Baker

Pacific Northwest National Laboratory

Lawrence Berkeley National Laboratory

mSphere

23795042 (eISSN)

Vol. 3 6 e00541-18

Subject Categories

Cell Biology

Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)

Genetics

DOI

10.1128/mSphere.00541-18

PubMed

30518677

More information

Latest update

3/21/2023