DNA Methylation Is Responsive to the Environment and Regulates the Expression of Biosynthetic Gene Clusters, Metabolite Production, and Virulence in Fusarium graminearum.

Christopher Bonner,Owen Rowland,Amanda Sproule,Rajagopal Subramaniam,David Overy

doi:10.3389/ffunb.2020.614633

Abstract

Histone modifications play a significant role in the regulation of biosynthetic gene clusters (BGCs) in the phytopathogen Fusarium graminearum, by contrast, epigenetic regulation by DNA methyltransferases (DNMTs) is less documented. In this study, we characterized two DNMTs (FgDIM-2 and FgRID) in F. graminearum, with homologies to "Deficient in methylation" (DIM-2) and "Repeat-induced point (RIP) deficient" (RID) from Neurospora. The loss of DNMTs resulted in not only a decrease in average methylation density in the nutrient-poor, compared to nutrient-rich conditions, but also differences in the genes expressed between the WT and the DNMT mutant strains, implicating the external environment as an important trigger in altering DNA methylation patterns. Consequently, we observed significant changes in the regulation of multiple BGCs and alterations in the pathogenicity of the fungus.

Highlights

In eukaryotes, epigenetics can be described broadly as changes in geneactivity, without changes to the underlying genetic code (Cavalli and Heard, 2019)
Two genes encoding putative DNA methyltransferases (DNMTs) have been identified in F. graminearum, no functional studies were conducted (Bewick et al, 2019)
Maximumlikelihood phylogenetic analysis of 35 DNMTs from 29 eukaryotic species (16 fungi, 12 mammals, 1 plant) and 1 prokaryotic species (E. coli) was undertaken to understand the evolutionary origins of DNMTs identified in F. graminearum (Supplementary Figures 1A,B)

Summary

Introduction

Epigenetics can be described broadly as changes in geneactivity, without changes to the underlying genetic code (Cavalli and Heard, 2019) This definition encompasses a wide variety of mechanisms including histone modification and DNA methylation (Wang et al, 2017; Cavalli and Heard, 2019). Studies have revealed the importance of epigenetics in gene regulation in fungi, both at the individual gene and at the genome level through chromatin remodeling with the formation of heterochromatin structures (Strauss and Reyes-Dominguez, 2011) This process is largely dictated by post-translation modifications of histones by methylation, and acetylation, and the methylation of DNA. Both regulation and dysregulation of enzymes such as histone methyltransferases and demethylases involved in post-translational modifications of histone residues contribute to the etiology of disease states (Kalish et al, 2014)

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Results

Conclusion