How does chromatin structure influence nuclear localization of chromosomes and genome stability?
Final Report Abstract
Facultative heterochromatin contains genes important for specific developmental or life cycle stages. Transcriptional regulation of these genes is influenced by chromatin structure. Facultative heterochromatin controls development and differentiation in many eukaryotes. In metazoans, plants, and many filamentous fungi, facultative heterochromatin is characterized by transcriptional repression and enrichment with nucleosomes that are trimethylated at histone H3 lysine 27 (H3K27me3). While loss of H3K27me3 results in derepression of transcriptional gene silencing in many species, additional up- and downstream layers of regulation are necessary to mediate control of transcription in chromosome regions enriched with H3K27me3. Here, we investigated the effects of one histone mark on histone H4, namely H4K20me3, in the fungus Zymoseptoria tritici, a globally important pathogen of wheat. Deletion of kmt5, the gene encoding the sole methyltransferase responsible for H4K20 methylation, resulted in global derepression of transcription, especially in regions of facultative heterochromatin. Reversal of silencing in the absence of H4K20me3 not only affected genes but also a large number of novel, previously undetected, non-coding transcripts generated from regions of facultative heterochromatin on accessory chromosomes. Transcriptional activation in kmt5 deletion strains was accompanied by a complete loss of Ash1-mediated H3K36me3 and chromatin reorganization affecting H3K27me3 and H3K4me2 distribution in regions of facultative heterochromatin. Strains with a H4K20M mutation in the single histone H4 gene of Z. tritici recapitulated these chromatin changes, suggesting that H4K20me3 is essential for Ash1- mediated H3K36me3. The Δkmt5 mutants we obtained are more sensitive to genotoxic stressors and both, Δkmt5 and Δash1, showed greatly increased rates of accessory chromosome loss. We conducted the first genome-wide assessment of H4K20 methylation levels in a fungus, and our discoveries reveal that multiple chromatin modifications are required to establish transcriptional silencing, providing the framework to understand epistasis relationships among these histone marks. Taken together, our results provide insights into a novel, and unsuspected, mechanism controlling the assembly and maintenance of facultative heterochromatin.
Publications
- 4th Uppsala Transposon Symposium (virtual, September 30 – October 02, 2020) "Recent loss of a DNA methyltransferase decreases mutations in repeats and impacts genome evolution in a fungal pathogen"
- Department of Botany and Plant Pathology (Oregon State University, USA, Jan. 30, 2020) Invited Seminar: "The impact of chromatin structure on genome stability and evolution in plant pathogens"
- Polycomb Repression without Bristles: Facultative Heterochromatin and Genome Stability in Fungi. Genes
Ridenour JB; Möller M; Freitag M.
(See online at https://doi.org/10.3390/genes11060638) - Recent loss of the Dim2 DNA methyltransferase decreases mutation rate in repeats and changes evolutionary trajectory in a fungal pathogen. PLOS Genetics
Möller M, Habig M, Lorrain C, Feurtey A, Haueisen J, Fagundes WC, Alizadeh A, Freitag M, Stukenbrock EH
(See online at https://doi.org/10.1371/journal.pgen.1009448) - 31st Fungal Genetics Conference (Pacific Grove, USA, March 15 – 20, 2022) Invited talk and poster: "Methylation of H4 controls gene expression in facultative heterochromatin"
- Group Seminar (University of Sydney, Australia, December 7, 2022) Seminar: “Chromatin structure and DNA methylation as drivers of intraspecies genome variability and evolution in a fungal plant pathogen”
- Plant Science Seminar Series (virtual, Australian National University, Canberra, September 28, 2022) Invited Seminar: "Chromatin structure and DNA methylation as drivers of intraspecies genome variability and evolution in a fungal plant pathogen"
- Stromlo Plant Pathology meeting (Australian National University, Canberra, Australia, December 1-2, 2022) Talk: “Recent loss of the Dim2 DNA methyltransferase decreases mutation rate in repeats and changes evolutionary trajectory in a fungal pathogen”
