Fungal epigenetics
Overview
Overview
We are focusing on molecular genetics of filamentous fungi with emphasis on secondary metabolism (e.g. mycotoxin production), secondary metabolite (SM) biosynthesis and gene regulation in the context of chromatin, as well as the interplay of chromatin with global transcription factors known to affect SM biosynthesis. Next to this, we are interested in the identification of new SMs (e.g. by altering the chromatin structure) and the functional characterization of the involved biosynthetic genes.
Leader: Dr. Lena Studt-Reinhold
Research
Fungi are known to produce a plethora of chemical compounds (so-called secondary metabolites, SMs). Some have toxic or carcinogenic properties, while others are applied in agriculture or medicine (e.g. antibiotics). Advances in genome sequencing combined with algorithms involved in mining SM biosynthetic gene clusters have shown that fungi have the genetic capacity to produce a much higher number of SMs than previously anticipated. Limitations to exploit the full genetic potential of SM-producing fungi arise from the fact that only a fraction of them is produced under standard laboratory conditions, leaving the vast majority of SMs yet to be identified. Thus, understanding the regulation of SM production, and designing approaches to quickly make them useful is a key challenge in this field of study.
It is now well established that changes in the chromatin structure (e.g. by deposition of histone marks or histone variants) play a key role in regulating fungal SM gene expression. Though many histone marks seem to affect SM gene expression in some way, the underlying regulatory mechanisms remain largely elusive. We aim to reach a better understanding on how this is achieved by exploring chromatin-level regulation of fungal SM biosynthetic gene clusters using Fusarium species as a model system.
We apply state-of-the-art molecular techniques and biochemistry combined with whole genome approaches (transcriptome, metabolome and epigenome analyses) that allow to determine the chromatin dynamics of SM biosynthetic gene clusters responding to different environmental stimuli.
Current projects
EPIVIT is dedicated to determine the role, function and histone crosstalk of the histone methyltransferase Kmt6 in Fusarium species.
In Fusarium fujikuroi, trimethylation of histone 3 lysine 27 (H3K27me3) – a hallmark of facultative heterochromatin – functions in SM gene silencing. In contrast to published filamentous fungi, loss of H3K27me3 is lethal in this fungus. Knock-down of FfKMT6 involved in H3K27me3 by RNA Interference resulted in reduced H3K27me3 levels accompanied by crippled growth, abolished conidiation and increased SM biosynthesis. Intriguingly, reversion phenotypes occurred that showed elevated FfKMT6 expression and restored wild type-like growth and conidiation.
The goal of EPIVIT is to gain deeper knowledge on Kmt6-mediated gene silencing in members of the Fusarium fujikuroi species complex (FFSC). This will be achieved by (1) Evaluating whether Kmt6 vitality is conserved within members of the FFC; (2) Unraveling the cause that sets F. fujikuroi (or the FFSC) apart from other fungal species; and (3) Exploiting the relationship between H3K27me3 and other relevant histone marks (histone crosstalk).
HISTOVAR aims at characterizing the yet unexplored histone variant H2A.Z in phytopathogenic fusaria.
Among known eukaryotic histone marks, although regularly found as decorating transcriptionally active genes, the role of the variant H2A.Z still remains a riddle, with conflictual roles often described for the same organisms. The current project is focused on the chromatin dynamics in the two prominent Fusarium spp., Fusarium fujikuroi and Fusarium graminearum, infecting rice and wheat, respectively, to study the role of so far overlooked – but likely essential – mechanisms involving H2A.Z during secondary metabolism and pathogenesis.
HISTOVAR is a collaborative project between an Austrian and a French research group (Joint Project). We aim at: (1) Identifying the role of H2A.Z in development, pathogenicity, and SM; (2) Mapping the positions of H2A.Z in the genomes relative to the positions of all nucleosomes, to positively identify genomic segments under its influence; and (3) Understanding the relationship between H2A.Z and relevant activating and silencing histone marks in both fungi.
Selected Publications
Atanasoff-Kardjalieff AK, Lünne F, Kalinina S, Strauss J, Humpf HU, Studt L (2021) Biosynthesis of fusapyrone depends on the H3K9 methyltransferase, FmKmt1, in Fusarium mangiferae. Front Fungal Biol. 2:671796. doi: 10.3389/ffunb.2021.671796.
Bachleitner S, Sulyok M, Sørensen JL, Strauss J, Studt L (2021) The H4K20 methyltransferase Kmt5 is involved in secondary metabolism and stress response in phytopathogenic Fusarium species. Fungal Genet Biol. 155:103602 doi: 10.1016/j.fgb.2021.103602.
Chen Z, Zehraoui E, Atanasoff-Kardjalieff AK, Strauss J, Studt L, Ponts N (2020) Effect of H2A.Z deletion is rescued by compensatory mutations in Fusarium graminearum. PLoS Genet. 16:e1009125. doi:10.1371/journal.pgen.1009125
Janevska S, Güldener U, Sulyok M, Tudzynski B, Studt L (2018) Set1 and Kdm5 are antagonists for H3K4 methylation and regulators of the major conidiation-specific transcription factor gene ABA1 in Fusarium fujikuroi. Environ Microbiol. 20:3343‐3362. doi:10.1111/1462-2920.14339.
Studt L, Janevska S, Arndt B, Boedi S, Sulyok M, Humpf HU, Tudzynski B, Strauss J (2017) Lack of the COMPASS Component Ccl1 reduced H3K4 trimethylation levels and affects transcription of secondary metabolite genes in two plant-pathogenic Fusarium species. Front Microbiol. 7:2144. doi: 10.3389/fmicb.2016.02144.
Niehaus EM, Studt L, von Bargen KW, Kummer W, Humpf HU, Reuter G, Tudzynski B (2016) Sound of Silence: the beauvericin cluster in Fusarium fujikuroi is controlled by cluster-specific and global regulators mediated by H3K27 modification. Environ Microbiol. 18:4282-4302. doi: 10.1111/1462-2920.13576.
Studt L, Rösler SM, Burkhardt I, Arndt B, Freitag M, Humpf HU, Dickschat JS, Tudzynski B (2016) Knock-down of the methyltransferase Kmt6 relieves H3K27me3 and results in induction of cryptic and otherwise silent secondary metabolite gene clusters in Fusarium fujikuroi. Environ Microbiol. 18:4037-4054. doi: 10.1111/1462-2920.13427.
Wiemann P, Sieber CM, von Bargen KW, Studt L, Niehaus EM, Espino JJ, Huß K, Michielse CB, Albermann S, Wagner D, Bergner SV, Connolly LR, Fischer A, Reuter G, Kleigrewe K, Bald T, Wingfield BD, Ophir R, Freeman S, Hippler M, Smith KM, Brown DW, Proctor RH, Münsterkötter M, Freitag M, Humpf HU, Güldener U, Tudzynski B (2013) Deciphering the cryptic genome: genome-wide analyses of the rice pathogen Fusarium fujikuroi reveal complex regulation of secondary metabolism and novel metabolites. PLoS Pathog., 9:e1003475. doi:10.1371/journal.ppat.1003475
