Putative methyltransferase LaeA and transcription factor CreA are necessary for proper asexual development and controlling secondary metabolic gene cluster expression

The morphological development of fungi is a complex process and is often coupled with secondary metabolite production. In this study, we assessed the function of putative methyltransferase LaeA and transcription factor CreA in controlling asexual development and secondary metabolic gene cluster expression in Penicillium oxalicum. The deletion of laeA (Delta laeA) impaired the conidiation in P. oxalicum, with a downregulated expression of brlA. Overexpression of P. oxalicum brlA in Delta laeA could upregulate brlA and abaA remarkably, but could not rescue the conidiation defect; therefore, brlA and abaA expression were necessary but not sufficient for conidiation. Deletion of creA in Delta laeA background (Delta laeA Delta creA) blocked conidiation with a white fluffy phenotype. Nutrient-rich medium could not rescue developmental defects in Delta laeA Delta creA mutant but could rescue defects in Delta laeA. Expression of 10 genes, namely, albA/wA, abrB/yA, arpA, aygA, arpA-like, arpB, arpB-like, rodA, rodA-like, and rodB, for pigmentation and spore wall protein genes was silenced in Delta laeA Delta creA, whereas only six of them were downregulated in Delta laeA. Among the 28 secondary metabolism gene clusters in P. oxalicum, four secondary metabolism gene clusters were silenced in Delta laeA and two were also silenced in Delta brlA mutant. A total of 10 physically linked and coregulated genes were distributed over five chromosomes in Delta laeA. Six of these genes were located in subtelomeric regions, thus demonstrating a positional bias for LaeA-regulated clusters toward subtelomeric regions. All of silenced clusters located in subtelomeric regions were derepressed in Delta laeA Delta creA, hence showing that lack of CreA could remediate the repression of gene clusters in Delta laeA background. Results show that both putative methyltransferase LaeA and transcription factor CreA are necessary for proper asexual development and controlling secondary metabolic gene cluster expression. (C) 2016 Elsevier Inc. All rights reserved.