Author:

Palmer JM, Bok JW, Lee S, Dagenais TR, Andes DR, Kontoyiannis DP, Keller NP

Date: 16 May 2013

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 inà‚ Aspergillus nidulansà‚ 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 pathogenà‚ Aspergillus fumigatus. Although deletion ofà‚ hdmAà‚ showed no phenotype under the conditions tested, theà‚ cclAà‚ 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,à‚ àŽâ€cclAà‚ was sensitive to 6-azauracil indicating a defect in transcriptional elongation. Despite the poor growth, theà‚ àŽâ€cclAà‚ mutant had wild-type pathogenicity in a murine model and theà‚ 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 inà‚ A. fumigatus, however does not contribute to pathogenicity under the conditions tested.

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