Influence of H3K9 methylation on gene mutation rates in yeast: Advancing epigenetic research with controlled experimental design

Abstract

Mutations drive genetic variation, fueling both oncogenesis and species evolution. The mutation rate varies across the genome, potentially influenced by chromatin organization through histone modifications and other factors. However, the precise relationship between chromatin structure and mutation rate remains poorly understood and needs further investigation. One such modification, the methylation of histone H3 at lysine 9 (H3K9me), is known to form heterochromatin and repress transcription in euchromatin, thereby maintaining genome stability essential for organism survival. This study aimed to elucidate the effect of H3K9 methylation, in isolation from other histone markers, on the mutation rate in fission yeast. Employing fluctuation assays and statistical analysis, our innovative methodology estimates the mutation rates of a single gene under two different conditions within a single experiment using an isogenic clone in Fission yeast. Our findings highlight a potential association between H3K9 methylation and the phenotypic mutation rate of the same gene, ura4⁺. For prospective researchers, this study introduces a new experimental approach that offers unprecedented accuracy in gene analysis, with implications for both genetic research and epigenetic therapy.