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

ABSTRACT:

Background

CRISPR-Cas9 genome editing enables precise genetic modifications by introducing targeted DNA double-strand breaks (DSBs). While Cas9-induced DSBs are known to cause unintended on-target mutations, their impact on the epigenetic landscape remains unexplored.

Results

Here, we investigate how Cas9-induced DSBs affect DNA methylation patterns in human embryonic stem cells (hESCs). We induce DSBs at differentially methylated regions of imprinted genomic loci and perform high-coverage, long-read native DNA sequencing to simultaneously obtain genetic variant and base-resolution methylation data in a haplotype-resolved manner. Our findings reveal that DSBs cause significant changes in DNA methylation at target sites through mechanisms including homologous recombination, l

SUBMITTER: Wang M 

PROVIDER: S-EPMC12673772 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature