CRISPR-Cas9-induced double-strand breaks disrupt maintenance of epigenetic information

This study shows that CRISPR-Cas9 double-strand breaks can cause lasting changes in local DNA-methylation patterns — revealing that genome editing affects not only DNA sequences but also the epigenome. Using Oxford Nanopore Cas9 enrichment and their custom analysis pipelines, the team found that breaks at imprinted loci in human stem cells led to persistent methylation loss linked to homologous recombination, large structural variants, and impaired methylation maintenance. Similar effects were observed in heterochromatin regions and cancer cells, suggesting a general connection between DNA breaks and epigenetic instability. To the authors' knowledge, the first demonstration that genome editing can disrupt epigenetic information, with implications for aging, cancer, and therapeutic genome engineering.

Read more in this KAUST Discovery article