Destabilization of chromosome structure by histone H3 lysine 27 methylation

PLoS Genetics, Journal Year: 2019, Volume and Issue: 15(4), P. e1008093 - e1008093

Published: April 22, 2019

Chromosome and genome stability are important for normal cell function as instability often correlates with disease dysfunction of DNA repair mechanisms. Many organisms maintain supernumerary or accessory chromosomes that deviate from standard chromosomes. The pathogenic fungus Zymoseptoria tritici has many eight chromosomes, which highly unstable during meiosis mitosis, transcriptionally repressed, show enrichment repetitive elements, heterochromatic histone methylation marks, e.g., trimethylation H3 lysine 9 27 (H3K9me3, H3K27me3). To elucidate the role heterochromatin on in Z. tritici, we deleted genes encoding methyltransferases responsible H3K9me3 H3K27me3, kmt1 kmt6, respectively, generated a double mutant. We combined experimental evolution genomic analyses to determine impact these deletions chromosome stability, both vitro planta. used whole sequencing, ChIP-seq, RNA-seq compare changes chromatin structure, differences gene expression between mutant wildtype strains. Analyses ChIP-seq data H3K9me3-deficient strains revealed dramatic reorganization, where H3K27me3 is mostly relocalized into regions enriched wild type. rearrangements formation new were found absence H3K9me3, accompanied by activation transposable elements. In stark contrast, loss actually increased under growth conditions vitro, even without large scale activity. conclude maintenance because it disallows considered constitutive heterochromatin. this system, reduces overall generating "metastable" state quasi-essential genome.

Language: Английский

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Epigenetic modifications affect the rate of spontaneous mutations in a pathogenic fungus

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: Oct. 7, 2021

Abstract Mutations are the source of genetic variation and substrate for evolution. Genome-wide mutation rates appear to be affected by selection probably adaptive. Mutation also known vary along genomes, possibly in response epigenetic modifications, but causality is only assumed. In this study we determine direct impact modifications temperature stress on mitotic a fungal pathogen using accumulation approach. Deletion mutants lacking confirm that histone mark H3K27me3 increases whereas H3K9me3 decreases rate. Furthermore, cytosine methylation transposable elements (TE) rate 15-fold resulting significantly less TE mobilization. Also accessory chromosomes have higher rates. Finally, find substantially elevates Taken together, environmental conditions modify location spontaneous mutations genome alter its evolutionary trajectory.

Language: Английский

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Histone modification dynamics at H3K27 are associated with altered transcription of in planta induced genes in Magnaporthe oryzae

PLoS Genetics, Journal Year: 2021, Volume and Issue: 17(2), P. e1009376 - e1009376

Published: Feb. 3, 2021

Transcriptional dynamic in response to environmental and developmental cues are fundamental biology, yet many mechanistic aspects poorly understood. One such example is fungal plant pathogens, which use secreted proteins small molecules, termed effectors, suppress host immunity promote colonization. Effectors highly expressed planta but remain transcriptionally repressed ex , our understanding of these transcriptional dynamics remains limited. We tested the hypothesis that repressive histone modification at H3-Lys27 underlies silencing exchange for an active chemical contributes transcription induced genes. Using genetics, chromatin immunoprecipitation sequencing RNA-sequencing, we determined H3K27me3 provides significant local repression. detail how regions lose gain H3K27ac, changes associated with increased transcription. Importantly, observed genes were marked by during axenic growth, altered H3K27 influences ChIP-qPCR growth suggests modifications generally stable, can undergo specific genomic locations. Our results support genome regulation specifically important infection.

Language: Английский

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DNA methylation across the tree of life, from micro to macro-organism

Bioengineered, Journal Year: 2022, Volume and Issue: 13(1), P. 1666 - 1685

Published: Jan. 1, 2022

DNA methylation is a process in which methyl (CH3) groups are added to the molecule. The segment does not change sequence, but could alter action of DNA. Different enzymes like methyltransferases (DNMTs) take part cytosine/adenine nucleosides In prokaryotes, performed prevent attack phage and also plays role chromosome replication repair. fungi, studied see transcriptional changes, as insects, that well-known, it different other organisms. mammals, related types cancers most important placental development abnormal connected with diseases cancer, autoimmune diseases, rheumatoid arthritis.

Language: Английский

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Recent transposable element bursts are associated with the proximity to genes in a fungal plant pathogen

PLoS Pathogens, Journal Year: 2023, Volume and Issue: 19(2), P. e1011130 - e1011130

Published: Feb. 14, 2023

The activity of transposable elements (TEs) contributes significantly to pathogen genome evolution. TEs often destabilize integrity but may also confer adaptive variation in pathogenicity or resistance traits. De-repression epigenetically silenced initiates bursts transposition that be counteracted by purifying selection and defenses. However, how these forces interact determine the expansion routes within a species remains largely unknown. Here, we analyzed set 19 telomere-to-telomere genomes fungal wheat Zymoseptoria tritici. Phylogenetic reconstruction ancestral state estimates individual TE families revealed have undergone distinct activation repression periods resulting highly uneven copy numbers between same species. Most are clustered gene poor niches, indicating strong against insertions near coding sequences, as consequence insertion site preferences. with high low sequence divergence signatures defense mechanisms (i.e., RIP). In contrast, small non-autonomous MITEs) less impacted located close proximity genes. Individual experienced multiple burst events generated many nearly identical copies. We found Copia element was initiated from recent copies inserted substantially closer genes compared older Overall, tended initiate GC-rich niches escaped inactivation genomic Our work shows specific environments features provide triggers for proliferation genomes.

Language: Английский

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Lessons on fruiting body morphogenesis from genomes and transcriptomes of Agaricomycetes

Studies in Mycology, Journal Year: 2023, Volume and Issue: 104(1), P. 1 - 85

Published: Feb. 1, 2023

Language: Английский

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Molecular regulation of fungal secondary metabolism

World Journal of Microbiology and Biotechnology, Journal Year: 2023, Volume and Issue: 39(8)

Published: May 20, 2023

Language: Английский

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Chromatin-dependent regulation of secondary metabolite biosynthesis in fungi: is the picture complete?

FEMS Microbiology Reviews, Journal Year: 2019, Volume and Issue: 43(6), P. 591 - 607

Published: June 19, 2019

ABSTRACT Fungal secondary metabolites are small molecules that exhibit diverse biological activities exploited in medicine, industry and agriculture. Their biosynthesis is governed by co-expressed genes often co-localize gene clusters. Most of these metabolite clusters inactive under laboratory conditions, which due to a tight transcriptional regulation. Modifications chromatin, the complex DNA histone proteins influencing accessibility, play an important role this However, tinkering with well-characterised chemical genetic modifications affect chromatin alters expression only few biosynthetic clusters, thus regulation vast majority pathways remains enigmatic. In past, attempts activate silent fungi mainly focused on acetylation methylation, while other eukaryotes many post-translational involved transcription Thus, how regulates largely unexplored research field. review, we argue focusing significantly hampering our understanding chromatin-based Research underexplored interplay between different timely fully explore untapped reservoir fungal metabolites.

Language: Английский

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Effector gene silencing mediated by histone methylation underpins host adaptation in an oomycete plant pathogen

Nucleic Acids Research, Journal Year: 2019, Volume and Issue: 48(4), P. 1790 - 1799

Published: Nov. 29, 2019

Abstract The relentless adaptability of pathogen populations is a major obstacle to effective disease control measures. Increasing evidence suggests that gene transcriptional polymorphisms are strategy deployed by pathogens evade host immunity. However, the underlying mechanisms plasticity remain largely elusive. Here we found soybean root rot Phytophthora sojae evades Resistance Rps1b through in effector Avr1b occur absence any sequence variation. Elevated levels histone H3 Lysine27 tri-methylation (H3K27me3) were observed at locus naturally occurring Avr1b-silenced strain but not an Avr1b-expressing strain, suggesting correlation between this epigenetic modification and silencing Avr1b. To genetically test hypothesis, edited gene, PsSu(z)12, encoding core subunit H3K27me3 methyltransferase complex using CRISPR/Cas9, obtained three deletion mutants. depletion within genomic region correlated with impaired these Importantly, mutants lost ability immune recognition soybeans carrying Rps1b. These data support model which associated changes chromatin marks, highlighting variation as mechanism adaptive plasticity.

Language: Английский

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Recent loss of the Dim2 DNA methyltransferase decreases mutation rate in repeats and changes evolutionary trajectory in a fungal pathogen

PLoS Genetics, Journal Year: 2021, Volume and Issue: 17(3), P. e1009448 - e1009448

Published: March 22, 2021

DNA methylation is found throughout all domains of life, yet the extent and function differ among eukaryotes. Strains plant pathogenic fungus Zymoseptoria tritici appeared to lack cytosine (5mC) because gene amplification followed by Repeat-Induced Point mutation (RIP) resulted in inactivation dim2 methyltransferase gene. 5mC is, however, present closely related sister species. We demonstrate that occurred recently as some Z . isolates carry a functional Moreover, we show different path than previously hypothesized. mapped genome-wide distribution strains with or without alleles. Presence correlates high levels transposable elements (TEs), suggesting role genome defense. identified low carrying non-functional alleles, maintained over time, presumably an active Dnmt5 methyltransferase. Integration allele mutated restored normal levels, demonstrating de novo activity Dim2. To assess importance for evolution, performed evolution experiment, comparing genomes lacking presence alters nucleotide composition promoting C T transitions (C→T) specifically at CpA (CA) sites during mitosis, likely contributing TE inactivation. Our results density TEs polymorphic trait populations can impact evolution.

Language: Английский

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