title: Hsf1 and Hsp90 orchestrate temperature-dependent global transcriptional remodelling and chromatin architecture in Candida albicans.
abstract: Fever is a universal response to infection, and opportunistic pathogens such as Candida albicans have evolved complex circuitry to sense and respond to heat. Here we harness RNA-seq and ChIP-seq to discover that the heat shock transcription factor, Hsf1, binds distinct motifs in nucleosome-depleted promoter regions to regulate heat shock genes and genes involved in virulence in C. albicans. Consequently, heat shock increases C. albicans host cell adhesion, damage and virulence. Hsf1 activation depends upon the molecular chaperone Hsp90 under basal and heat shock conditions, but the effects are opposite and in part controlled at the level of Hsf1 expression and DNA binding. Finally, we demonstrate that Hsp90 regulates global transcription programs by modulating nucleosome levels at promoters of stress-responsive genes. Thus, we describe a mechanism by which C. albicans responds to temperature via Hsf1 and Hsp90 to orchestrate gene expression and chromatin architecture, thereby enabling thermal adaptation and virulence.
authors.affiliation: Aberdeen Fungal Group, University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen AB25 2ZD, UK.|Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada M5S 1A8.
authors.forename: Michelle D
authors.initials: MD
authors.lastname: Leach
authors.affiliation: Genome Sequencing and Analysis Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.
authors.forename: Rhys A
authors.initials: RA
authors.lastname: Farrer
authors.affiliation: Faculty of Health Sciences, University of Macau, Macau SAR 999078, China.
authors.forename: Kaeling
authors.initials: K
authors.lastname: Tan
authors.affiliation: Faculty of Health Sciences, University of Macau, Macau SAR 999078, China.
authors.forename: Zhengqiang
authors.initials: Z
authors.lastname: Miao
authors.affiliation: Department of Molecular and Biomedical Sciences, University of Maine, Orono, Maine 04469, USA.
authors.forename: Louise A
authors.initials: LA
authors.lastname: Walker
authors.affiliation: Genome Sequencing and Analysis Program, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.
authors.forename: Christina A
authors.identifier: 0000-0002-5778-960X
authors.initials: CA
authors.lastname: Cuomo
authors.affiliation: Department of Molecular and Biomedical Sciences, University of Maine, Orono, Maine 04469, USA.
authors.forename: Robert T
authors.identifier: 0000-0003-3223-7021
authors.initials: RT
authors.lastname: Wheeler
authors.affiliation: Aberdeen Fungal Group, University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen AB25 2ZD, UK.
authors.forename: Alistair J P
authors.initials: AJ
authors.lastname: Brown
authors.affiliation: Faculty of Health Sciences, University of Macau, Macau SAR 999078, China.
authors.forename: Koon Ho
authors.initials: KH
authors.lastname: Wong
authors.affiliation: Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada M5S 1A8.
authors.forename: Leah E
authors.initials: LE
authors.lastname: Cowen
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000235:genetics; D002176:Candida albicans / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity; D002843:Chromatin / Q000235:genetics* / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics* / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D000076249:Heat Shock Transcription Factors / Q000235:genetics* / Q000378:metabolism; D006358:Hot Temperature; D009036:Moths / Q000382:microbiology; D009707:Nucleosomes / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D013696:Temperature; D014774:Virulence / Q000235:genetics; D015027:Zebrafish / Q000382:microbiology
chemical_list: D002843:Chromatin; D005656:Fungal Proteins; D018841:HSP90 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D009707:Nucleosomes