Genome-wide redistribution of H3K27me3 is linked to genotoxic stress and defective growth. Neurospora crassa

H3K9 methylation directs heterochromatin formation by recruiting multiple HP1-containing complexes that deacetylate histones and methylate cytosine bases in DNA. In Neurospora crassa, a single H3K9 methyltransferase complex, DCDC, is required for normal growth and development. DCDC-deficient mutants are hypersensitive to the genotoxic agent methyl methanesulfonate (MMS), but the molecular basis of genotoxic stress is unclear. We found that both the MMS-sensitivity and growth phenotypes of DCDC-deficient strains are suppressed by mutation of eed or set-7, encoding components of the H3K27 methyltransferase PRC2. H3K27me3 undergoes genome-wide redistribution to constitutive heterochromatin in DCDC- or HP1-deficient mutants, and introduction of an H3K27 missense mutation is sufficient to rescue phenotypes of DCDC-deficient strains. Accumulation of H3K27me3 in heterochromatin does not compensate for silencing. However, strains deficient for both DCDC and PRC2 exhibit synthetic sensitivity to the topoisomerase I inhibitor Camptothecin and accumulate *H2A at heterochromatin, suggesting PRC2 modulates the response to genotoxic stress.