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Rewiring of Signaling Networks Modulating Thermotolerance in the Human Pathogen Cryptococcus neoformans.

Publication ,  Journal Article
Yang, D-H; Jung, K-W; Bang, S; Lee, J-W; Song, M-H; Floyd-Averette, A; Festa, RA; Ianiri, G; Idnurm, A; Thiele, DJ; Heitman, J; Bahn, Y-S
Published in: Genetics
January 2017

Thermotolerance is a crucial virulence attribute for human pathogens, including the fungus Cryptococcus neoformans that causes fatal meningitis in humans. Loss of the protein kinase Sch9 increases C. neoformans thermotolerance, but its regulatory mechanism has remained unknown. Here, we studied the Sch9-dependent and Sch9-independent signaling networks modulating C. neoformans thermotolerance by using genome-wide transcriptome analysis and reverse genetic approaches. During temperature upshift, genes encoding for molecular chaperones and heat shock proteins were upregulated, whereas those for translation, transcription, and sterol biosynthesis were highly suppressed. In this process, Sch9 regulated basal expression levels or induced/repressed expression levels of some temperature-responsive genes, including heat shock transcription factor (HSF1) and heat shock proteins (HSP104 and SSA1). Notably, we found that the HSF1 transcript abundance decreased but the Hsf1 protein became transiently phosphorylated during temperature upshift. Nevertheless, Hsf1 is essential for growth and its overexpression promoted C. neoformans thermotolerance. Transcriptome analysis using an HSF1 overexpressing strain revealed a dual role of Hsf1 in the oxidative stress response and thermotolerance. Chromatin immunoprecipitation demonstrated that Hsf1 binds to the step-type like heat shock element (HSE) of its target genes more efficiently than to the perfect- or gap-type HSE. This study provides insight into the thermotolerance of C. neoformans by elucidating the regulatory mechanisms of Sch9 and Hsf1 through the genome-scale identification of temperature-dependent genes.

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Published In

Genetics

DOI

EISSN

1943-2631

Publication Date

January 2017

Volume

205

Issue

1

Start / End Page

201 / 219

Location

United States

Related Subject Headings

  • Transcriptional Activation
  • Transcription Factors
  • Thermotolerance
  • Temperature
  • Signal Transduction
  • Phosphorylation
  • Molecular Chaperones
  • Heat-Shock Response
  • Heat-Shock Proteins
  • Heat Shock Transcription Factors
 

Citation

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Yang, D.-H., Jung, K.-W., Bang, S., Lee, J.-W., Song, M.-H., Floyd-Averette, A., … Bahn, Y.-S. (2017). Rewiring of Signaling Networks Modulating Thermotolerance in the Human Pathogen Cryptococcus neoformans. Genetics, 205(1), 201–219. https://doi.org/10.1534/genetics.116.190595
Yang, Dong-Hoon, Kwang-Woo Jung, Soohyun Bang, Jang-Won Lee, Min-Hee Song, Anna Floyd-Averette, Richard A. Festa, et al. “Rewiring of Signaling Networks Modulating Thermotolerance in the Human Pathogen Cryptococcus neoformans.Genetics 205, no. 1 (January 2017): 201–19. https://doi.org/10.1534/genetics.116.190595.
Yang D-H, Jung K-W, Bang S, Lee J-W, Song M-H, Floyd-Averette A, et al. Rewiring of Signaling Networks Modulating Thermotolerance in the Human Pathogen Cryptococcus neoformans. Genetics. 2017 Jan;205(1):201–19.
Yang, Dong-Hoon, et al. “Rewiring of Signaling Networks Modulating Thermotolerance in the Human Pathogen Cryptococcus neoformans.Genetics, vol. 205, no. 1, Jan. 2017, pp. 201–19. Pubmed, doi:10.1534/genetics.116.190595.
Yang D-H, Jung K-W, Bang S, Lee J-W, Song M-H, Floyd-Averette A, Festa RA, Ianiri G, Idnurm A, Thiele DJ, Heitman J, Bahn Y-S. Rewiring of Signaling Networks Modulating Thermotolerance in the Human Pathogen Cryptococcus neoformans. Genetics. 2017 Jan;205(1):201–219.

Published In

Genetics

DOI

EISSN

1943-2631

Publication Date

January 2017

Volume

205

Issue

1

Start / End Page

201 / 219

Location

United States

Related Subject Headings

  • Transcriptional Activation
  • Transcription Factors
  • Thermotolerance
  • Temperature
  • Signal Transduction
  • Phosphorylation
  • Molecular Chaperones
  • Heat-Shock Response
  • Heat-Shock Proteins
  • Heat Shock Transcription Factors