KdmA, a histone H3 demethylase with bipartite function, differentially regulates primary and secondary metabolism in Aspergillus nidulans

Abstract

Summary A spergillus nidulans kdmA encodes a member of the KDM4 family of jumonji histone demethylase proteins, highly similar to metazoan orthologues both within functional domains and in domain architecture. This family of proteins exhibits demethylase activity towards lysines 9 and 36 of histone H3 and plays a prominent role in gene expression and chromosome structure in many species. Mass spectrometry mapping of A . nidulans histones revealed that around 3% of bulk histone H3 carried trimethylated H3K9 (H3K9me3) but more than 90% of histones carried either H3K36me2 or H3K36me3. KdmA functions as H3K36me3 demethylase and has roles in transcriptional regulation. Genetic manipulation of KdmA levels is tolerated without obvious effect in most conditions, but strong phenotypes are evident under various conditions of stress. Transcriptome analysis revealed that – in submerged early and late cultures – between 25% and 30% of the genome is under KdmA influence respectively. Transcriptional imbalance in the kdm A deletion mutant may contribute to the lethal phenotype observed upon exposure of mutant cells to low‐density visible light on solid medium. Although KdmA acts as transcriptional co‐repressor of primary metabolism genes, it is required for full expression of several genes involved in biosynthesis of secondary metabolites.

Regulation of subtelomeric fungal secondary metabolite genes by H3K4me3 regulators CclA and KdmB

“…We also analyzed overexpression mutants of kdmA (EfM3.030120) encoding the E. festucae homologue of KDM4 (H3K9/K36 demethylase). In A. nidulans , demethylase activity of KdmA was only observed at the local gene level and not at the global level (Gacek‐Matthews et al , ). Likewise, we also did not observe a reduction in the global levels of H3K9 and H3K36 methylation in the E. festucae kdmA overexpression strains (Fig.…”

Chromatin‐level regulation of the fragmented dothistromin gene cluster in the forest pathogen Dothistroma septosporum

“…In A. nidulans , the biosynthesis of sterigmatocystin is associated with upregulation of the global regulator LaeA (Bok and Keller, ), which in turn activates transcription of the pathway regulator AflR. A. nidulans does not have a methyltransferase for H3K27 (Gacek‐Matthews et al ., ) but during the active phase of growth the sterigmatocystin gene cluster appeared to be marked by HepA and H3K9me3, which decreased on transition to the stationary phase, while H3K9/K14ac occupancy increased (Reyes‐Dominguez et al ., ). However, more recent studies suggest H3K9me3 is instead mainly confined to the borders of the sterigmatocystin cluster and its role in controlling sterigmatocystin gene expression is not clear (Gacek‐Matthews et al ., ).…”

“…However, more recent studies suggest H3K9me3 is instead mainly confined to the borders of the sterigmatocystin cluster and its role in controlling sterigmatocystin gene expression is not clear (Gacek‐Matthews et al ., ). Instead there is some enrichment for positive chromatin marks such as H3K4me3 and H3K36me3 within the gene cluster during the secondary metabolism phase, although these chromatin marks occurred at low levels compared to those in genes involved in primary metabolism (Gacek‐Matthews et al ., ; Gacek‐Matthews et al ., ). Chromatin modification by acetylation is also important in secondary metabolite pathway regulation in many filamentous fungi (Lan et al ., ).…”

“…Although not present in species of Aspergillus (Gacek‐Matthews et al ., ), another histone methylation mark, H3K27me3 (trimethylation of lysine 27 on histone 3) regulates secondary metabolite production in some fungi. In Fusarium graminearum and Epichloë festucae the histone H3K27 methyltransferase KMT6 affects expression of secondary metabolite gene clusters localized in subtelomeric regions (Connolly et al ., ; Chujo and Scott, ).…”

KdmA, a histone H3 demethylase with bipartite function, differentially regulates primary and secondary metabolism in Aspergillus nidulans

“…In the published version of Gacek‐Matthews et al . (), issue 96:4, the authors would like to amend the opening sentence in the Acknowledgement section:…”