title: Secondary metabolic gene cluster silencing in Aspergillus nidulans.
abstract: In contrast to most primary metabolism genes, the genes involved in secondary metabolism and certain nutrient utilization pathways are clustered in fungi. Recently a nuclear protein, LaeA, was found to be required for the transcription of several secondary metabolite gene clusters in Aspergillus nidulans. Here we show that LaeA regulation does not extend to nutrient utilization or the spoC1 sporulation clusters. One of the secondary metabolite clusters regulated by LaeA contains the positive regulatory (i.e. aflR) and biosynthetic genes required for biosynthesis of sterigmatocystin (ST), a carcinogenic toxin. Analysis of ST gene cluster expression indicates LaeA regulation of the cluster is location specific as transcription of genes bordering the ST cluster are unaffected in a DeltalaeA mutant and placement of a primary metabolic gene, argB, in the ST cluster resulted in argB silencing in the DeltalaeA background. ST cluster gene expression was remediated when an additional copy of aflR was placed outside of the cluster but not when placed in the cluster. Site-specific mutation of an s-adenosyl methionine (AdoMet) binding site in LaeA generated a DeltalaeA phenotype suggesting the protein to be a methyltransferase.
authors.affiliation: Department of Plant Pathology, University of Wisconsin--Madison, 1630 Linden Drive, WI 53706, USA.
authors.forename: Jin Woo
authors.initials: JW
authors.lastname: Bok
authors.forename: Daan
authors.initials: D
authors.lastname: Noordermeer
authors.forename: Shubha P
authors.initials: SP
authors.lastname: Kale
authors.forename: Nancy P
authors.initials: NP
authors.lastname: Keller
mesh_terms: D001233:Aspergillus nidulans / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D005656:Fungal Proteins / Q000235:genetics* / Q000502:physiology; D015966:Gene Expression Regulation, Fungal; D023061:Gene Order; D020868:Gene Silencing; D008745:Methylation; D005810:Multigene Family / Q000235:genetics; D011496:Protein Methyltransferases / Q000235:genetics / Q000502:physiology*; D011499:Protein Processing, Post-Translational; D013241:Sterigmatocystin / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
chemical_list: C113837:AFLR protein, Aspergillus; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D014157:Transcription Factors; D013241:Sterigmatocystin; D011496:Protein Methyltransferases