In contrast to primary metabolism, the genes involved in secondary metabolism 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 (Bok and Keller 2004). Here we show that regulation is confined to secondary metabolite clusters and not other defined metabolic clusters including proline, nitrate and ethanol utilization clusters. One of these clusters contains the positive regulatory (i.e. aflR) and biosynthetic genes required for biosynthesis of sterigmatocystin (ST), a carcinogenic toxin. Analysis of ST cluster expression indicates LaeA regulation of the cluster is location specific as transcription of genes bordering the ST cluster are unaffected in a delta laeA mutant and placement of a primary metabolic gene, argB, in the ST cluster resulted in argB silencing in the delta laeA background. ST cluster gene expression was remediated when an addition copy of aflR was placed outside of the cluster but not when placed in the cluster. Site specific mutation of a S-adenosyl methionine (AdoMet)-binding site in LaeA generated a delta laeA phenotype suggesting the protein to be a methyltransferase. We present a model of LaeA involvement in chromatin regulation of secondary metabolite gene clusters.
Full conference title:
23rd Fungal Genetics Conference
- Fungal Genetics Conference 23rd (2002)