title: Fungal Morphology, Iron Homeostasis, and Lipid Metabolism Regulated by a GATA Transcription Factor in Blastomyces dermatitidis.
abstract: In response to temperature, Blastomyces dermatitidis converts between yeast and mold forms. Knowledge of the mechanism(s) underlying this response to temperature remains limited. In B. dermatitidis, we identified a GATA transcription factor, SREB, important for the transition to mold. Null mutants (SREBΔ) fail to fully complete the conversion to mold and cannot properly regulate siderophore biosynthesis. To capture the transcriptional response regulated by SREB early in the phase transition (0-48 hours), gene expression microarrays were used to compare SREB∆ to an isogenic wild type isolate. Analysis of the time course microarray data demonstrated SREB functioned as a transcriptional regulator at 37°C and 22°C. Bioinformatic and biochemical analyses indicated SREB was involved in diverse biological processes including iron homeostasis, biosynthesis of triacylglycerol and ergosterol, and lipid droplet formation. Integration of microarray data, bioinformatics, and chromatin immunoprecipitation identified a subset of genes directly bound and regulated by SREB in vivo in yeast (37°C) and during the phase transition to mold (22°C). This included genes involved with siderophore biosynthesis and uptake, iron homeostasis, and genes unrelated to iron assimilation. Functional analysis suggested that lipid droplets were actively metabolized during the phase transition and lipid metabolism may contribute to filamentous growth at 22°C. Chromatin immunoprecipitation, RNA interference, and overexpression analyses suggested that SREB was in a negative regulatory circuit with the bZIP transcription factor encoded by HAPX. Both SREB and HAPX affected morphogenesis at 22°C; however, large changes in transcript abundance by gene deletion for SREB or strong overexpression for HAPX were required to alter the phase transition.
authors.affiliation: Department of Medicine, University of Wisconsin, Madison, Madison, Wisconsin, United States of America.
authors.forename: Amber J
authors.initials: AJ
authors.lastname: Marty
authors.affiliation: Department of Biostatistics and Medical Informatics, University of Wisconsin, Madison, Madison, Wisconsin, United States of America.
authors.forename: Aimee T
authors.initials: AT
authors.lastname: Broman
authors.affiliation: Department of Medicine, University of Wisconsin, Madison, Madison, Wisconsin, United States of America.
authors.forename: Robert
authors.initials: R
authors.lastname: Zarnowski
authors.affiliation: Department of Medicine, University of Wisconsin, Madison, Madison, Wisconsin, United States of America.
authors.forename: Teigan G
authors.initials: TG
authors.lastname: Dwyer
authors.affiliation: Department of Biochemistry, University of Wisconsin, Madison, Madison, Wisconsin, United States of America.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Bond
authors.affiliation: Université du Littoral Côte d'Opale, Unité de Chimie Environnementale et Interactions sur le Vivant, Calais, France.
authors.forename: Anissa
authors.initials: A
authors.lastname: Lounes-Hadj Sahraoui
authors.affiliation: Université du Littoral Côte d'Opale, Unité de Chimie Environnementale et Interactions sur le Vivant, Calais, France.
authors.forename: Joël
authors.initials: J
authors.lastname: Fontaine
authors.affiliation: Department of Biochemistry, Department of Nutritional Sciences, University of Wisconsin, Madison, Madison, Wisconsin, United States of America.
authors.forename: James M
authors.initials: JM
authors.lastname: Ntambi
authors.affiliation: Department of Biostatistics and Medical Informatics, University of Wisconsin, Madison, Madison, Wisconsin, United States of America; Department of Statistics, University of Wisconsin, Madison, Madison, Wisconsin, United States of America.
authors.forename: Sündüz
authors.initials: S
authors.lastname: Keleş
authors.affiliation: Department of Biostatistics and Medical Informatics, University of Wisconsin, Madison, Madison, Wisconsin, United States of America.
authors.forename: Christina
authors.initials: C
authors.lastname: Kendziorski
authors.affiliation: Department of Medicine, University of Wisconsin, Madison, Madison, Wisconsin, United States of America.
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Gauthier
mesh_terms: D001758:Blastomyces / Q000378:metabolism*; D005658:Fungi / Q000378:metabolism; D050980:GATA Transcription Factors / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal / Q000235:genetics; D005800:Genes, Fungal / Q000235:genetics; D006706:Homeostasis / Q000502:physiology*; D007501:Iron / Q000378:metabolism*; D050356:Lipid Metabolism / Q000235:genetics / Q000502:physiology*
chemical_list: D050980:GATA Transcription Factors; D007501:Iron