Histone H3K9 and H3K27 methylation regulates fungal alkaloid biosynthesis in a fungal endophyte–plant symbiosis

Abstract

SummaryEpichloë festucae is a filamentous fungus that forms a mutually beneficial symbiotic association with Lolium perenne. This endophyte synthesizes bioprotective lolitrems (ltm) and ergot alkaloids (eas) in planta but the mechanisms regulating expression of the corresponding subtelomeric gene clusters are not known. We show here that the status of histone H3 lysine 9 and lysine 27 trimethylation (H3K9me3/H3K27me3) at these alkaloid gene loci are critical determinants of transcriptional activity. Using ChIP-qPCR we found that levels of H3K9me3 and H3K27me3 were reduced at these loci in plant infected tissue compared to axenic culture. Deletion of E. festucae genes encoding the H3K9-(ClrD) or H3K27-(EzhB) methyltransferases led to derepression of ltm and eas gene expression under non-symbiotic culture conditions and a further enhancement of expression in the double deletion mutant. These changes in gene expression were matched by corresponding reductions in H3K9me3 and H3K27me3 marks. Both methyltransferases are also important for the symbiotic interaction between E. festucae and L. perenne. Our results show that the state of H3K9 and H3K27 trimethylation of E. festucae chromatin is an important regulatory layer controlling symbiosis-specific expression of alkaloid bioprotective metabolites and the ability of this symbiont to form a mutualistic interaction with its host.

3,6-Dihydroxyflavone Suppresses Breast Carcinogenesis by Epigenetically Regulating miR-34a and miR-21

“…Histone modifications are specifically characterized by the genomic regulatory regions, such as inactive promoters that are enriched in trimethylated H3 at lysine 27 (H3K27me3) or trimethylated H3 at lysine 9 (H3K9me3) and active promoter regions that are enriched in acetylated H3 at lysine 27 (H3K27ac; ref. 29). Our study showed that 3,6-DHF significantly affects the histone modification in breast cancer cells, lowering the H3K9-14ac on the miR-21 promoter, which may contribute to the downregulation of miR-21.…”

Genome-wide redistribution of H3K27me3 is linked to genotoxic stress and defective growth

“…However, redistribution of H3K27me3 requires H3K9me2 in this fungus (23). This may also be the case in E. festucae, where deletion of the H3K27 MTase ΔezhB does not rescue the growth defects of the H3K9 MTase-deficient mutant ΔclrD (22). In plants and animals, cross-talk between different heterochromatin components and the Pc system has been linked to cell type-specific changes in chromatin architecture, raising the possibility that different heterochromatin-based mechanisms could regulate H3K27me3 in different cells even within the same organism (71,81,82).…”

“…Pc components are absent from the model yeasts Saccharomyces cerevisiae and Schizosaccharyomyces pombe, whereas PRC1 appears to be absent from all fungi (19). PRC2 is present in some fungi, however, and H3K27me3 directs transcriptional repression of PRC2-target domains in Neurospora, Fusarium graminearum, Epichloë festucae, and Cryptococcus neoformans (19)(20)(21)(22)(23). Thus, the application of microbial genetic approaches to study the Pc system in fungi can provide mechanistic insights into this evolutionarily conserved chromatin regulatory system.…”

Enhancing Nonribosomal Peptide Biosynthesis in Filamentous Fungi

“…Since then, manipulation of LaeA has been used to identify and demarcate a number of NRPS-derived metabolites in a multitude of species [54]. Identified metabolites and corresponding gene clusters include penicillin [53, 55, 56], gliotoxin [53], terrequinone A [57, 58], NRPS9- and NRPS11-derived metabolites [59], fusarin C [60, 61], pseurotin [62], ochratoxin A [63], tyrosine-derived alkaloids [64], beauvericin [65], as well as lolitrem and ergot alkaloids [66]. …”