Persistent chromatin alterations and gene expression reprogramming follow widespread DNA damage in glioblastoma.

ABSTRACT: DNA damage from routine cellular processes or exogenous insults can have a lasting impact on gene regulation beyond genetic mutations. The prevailing paradigm for the consequences of DNA damage repair revolves around restoration of the original genetic sequence, but long-term changes in chromatin configuration, gene expression and DNA modifications have not been analyzed. We introduced numerous, simultaneous Cas9-mediated DNA double strand breaks (DSBs) at defined locations in human glioblastoma cells and tracked both non-genetic and genetic alterations over time. Megabase-scale genomic alterations that endured two weeks after the initial damage were detected, involving a shift from transiently increased intra-TAD interactions to persistent long range cis and trans contacts,

SUBMITTER: Modrek AS 

PROVIDER: S-EPMC12262309 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature