How does chromatin structure influence nuclear localization of chromosomes and genome stability?

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Genome stability is essential to maintain cellular viability and function. However, a high degree of genome variation and instability is often found in cells associated to disease (e.g. cancer cells) or organisms that are rapidly evolving in response to changing environmental conditions. Based on previous studies on genome diversity and the presence of certain histone modifications in highly divergent regions, I hypothesize that histone marks, especially H3K27me3, contribute to the observed variability by promoting genome instability. With this project, I want to determine how heterochromatin distribution contributes to genome instability by influencing nuclear interaction of chromatin and the occurrence of DNA damage in a comparative study of the filamentous fungal model organisms Zymoseptoria tritici, Fusarium graminearum, and Neurospora crassa. I will analyze the distribution of heterochromatin histone marks H3K9me3, H3K27me3, H3K36me3, and H4K20me3 in wildtype and deletion mutants of the respective histone-methyltransferases in the three species. Using ChIP-sequencing, detection of double-strand breaks and chromosome conformation capture, I will be able to determine heterochromatin dynamics and their influence on genome stability and nuclear chromatin interactions. This project will gain important novel insights into the role of chromatin organization and dynamics for genome stability and genome evolution in different species. These findings will be especially relevant to understand mechanisms of DNA instability in organisms or cells that exhibit a high degree of genome instability and variability such as plant, animal, or human pathogens, as well as cancer cells.