title: Loss of CclA, required for histone 3 lysine 4 methylation, decreases growth but increases secondary metabolite production in Aspergillus fumigatus.
abstract: Secondary metabolite (SM) production in filamentous fungi is mechanistically associated with chromatin remodeling of specific SM clusters. One locus recently shown to be involved in SM suppression in Aspergillus nidulans was CclA, a member of the histone 3 lysine 4 methylating COMPASS complex. Here we examine loss of CclA and a putative H3K4 demethylase, HdmA, in the human pathogen Aspergillus fumigatus. Although deletion of hdmA showed no phenotype under the conditions tested, the cclA deletant was deficient in tri- and di-methylation of H3K4 and yielded a slowly growing strain that was rich in the production of several SMs, including gliotoxin. Similar to deletion of other chromatin modifying enzymes, ΔcclA was sensitive to 6-azauracil indicating a defect in transcriptional elongation. Despite the poor growth, the ΔcclA mutant had wild-type pathogenicity in a murine model and the Toll-deficient Drosophila model of invasive aspergillosis. These data indicate that tri- and di-methylation of H3K4 is involved in the regulation of several secondary metabolites in A. fumigatus, however does not contribute to pathogenicity under the conditions tested.
authors: Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, Madison, WI, USA.
authors: Jonathan M
authors: JM
authors: Palmer
authors: Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, Madison, WI, USA.
authors: Jin Woo
authors: JW
authors: Bok
authors: Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, Madison, WI, USA.
authors: Seul
authors: S
authors: Lee
authors: Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, Madison, WI, USA.
authors: Taylor R T
authors: TRT
authors: Dagenais
authors: Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, Madison, WI, USA.
authors: David R
authors: DR
authors: Andes
authors: Department of Infectious Disease, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors: Dimitrios P
authors: DP
authors: Kontoyiannis
authors: Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, Madison, WI, USA.|Department of Bacteriology, University of Wisconsin-Madison, Madison, WI, USA.
authors: Nancy P
authors: NP
authors: Keller
keywords: 6-azauracil sensitivity; Aspergillus fumigatus; COMPASS complex; Gliotoxin; Growth and development; Histone methylation; Secondary metabolism
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