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Investigating Conservation of the Cell-Cycle-Regulated Transcriptional Program in the Fungal Pathogen, Cryptococcus neoformans.

Publication ,  Journal Article
Kelliher, CM; Leman, AR; Sierra, CS; Haase, SB
Published in: PLoS genetics
December 2016

The pathogenic yeast Cryptococcus neoformans causes fungal meningitis in immune-compromised patients. Cell proliferation in the budding yeast form is required for C. neoformans to infect human hosts, and virulence factors such as capsule formation and melanin production are affected by cell-cycle perturbation. Thus, understanding cell-cycle regulation is critical for a full understanding of virulence factors for disease. Our group and others have demonstrated that a large fraction of genes in Saccharomyces cerevisiae is expressed periodically during the cell cycle, and that proper regulation of this transcriptional program is important for proper cell division. Despite the evolutionary divergence of the two budding yeasts, we found that a similar percentage of all genes (~20%) is periodically expressed during the cell cycle in both yeasts. However, the temporal ordering of periodic expression has diverged for some orthologous cell-cycle genes, especially those related to bud emergence and bud growth. Genes regulating DNA replication and mitosis exhibited a conserved ordering in both yeasts, suggesting that essential cell-cycle processes are conserved in periodicity and in timing of expression (i.e. duplication before division). In S. cerevisiae cells, we have proposed that an interconnected network of periodic transcription factors (TFs) controls the bulk of the cell-cycle transcriptional program. We found that temporal ordering of orthologous network TFs was not always maintained; however, the TF network topology at cell-cycle commitment appears to be conserved in C. neoformans. During the C. neoformans cell cycle, DNA replication genes, mitosis genes, and 40 genes involved in virulence are periodically expressed. Future work toward understanding the gene regulatory network that controls cell-cycle genes is critical for developing novel antifungals to inhibit pathogen proliferation.

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Published In

PLoS genetics

DOI

EISSN

1553-7404

ISSN

1553-7390

Publication Date

December 2016

Volume

12

Issue

12

Start / End Page

e1006453

Related Subject Headings

  • Transcription, Genetic
  • Saccharomyces cerevisiae
  • Mitosis
  • Humans
  • Genetic Variation
  • Gene Regulatory Networks
  • Gene Expression Regulation, Fungal
  • Gene Expression Regulation, Developmental
  • Fungal Proteins
  • Evolution, Molecular
 

Citation

APA
Chicago
ICMJE
MLA
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Kelliher, C. M., Leman, A. R., Sierra, C. S., & Haase, S. B. (2016). Investigating Conservation of the Cell-Cycle-Regulated Transcriptional Program in the Fungal Pathogen, Cryptococcus neoformans. PLoS Genetics, 12(12), e1006453. https://doi.org/10.1371/journal.pgen.1006453
Kelliher, Christina M., Adam R. Leman, Crystal S. Sierra, and Steven B. Haase. “Investigating Conservation of the Cell-Cycle-Regulated Transcriptional Program in the Fungal Pathogen, Cryptococcus neoformans.PLoS Genetics 12, no. 12 (December 2016): e1006453. https://doi.org/10.1371/journal.pgen.1006453.
Kelliher CM, Leman AR, Sierra CS, Haase SB. Investigating Conservation of the Cell-Cycle-Regulated Transcriptional Program in the Fungal Pathogen, Cryptococcus neoformans. PLoS genetics. 2016 Dec;12(12):e1006453.
Kelliher, Christina M., et al. “Investigating Conservation of the Cell-Cycle-Regulated Transcriptional Program in the Fungal Pathogen, Cryptococcus neoformans.PLoS Genetics, vol. 12, no. 12, Dec. 2016, p. e1006453. Epmc, doi:10.1371/journal.pgen.1006453.
Kelliher CM, Leman AR, Sierra CS, Haase SB. Investigating Conservation of the Cell-Cycle-Regulated Transcriptional Program in the Fungal Pathogen, Cryptococcus neoformans. PLoS genetics. 2016 Dec;12(12):e1006453.

Published In

PLoS genetics

DOI

EISSN

1553-7404

ISSN

1553-7390

Publication Date

December 2016

Volume

12

Issue

12

Start / End Page

e1006453

Related Subject Headings

  • Transcription, Genetic
  • Saccharomyces cerevisiae
  • Mitosis
  • Humans
  • Genetic Variation
  • Gene Regulatory Networks
  • Gene Expression Regulation, Fungal
  • Gene Expression Regulation, Developmental
  • Fungal Proteins
  • Evolution, Molecular