Senescence-activated enhancer landscape orchestrates the senescence-associated secretory phenotype in murine fibroblasts.

ABSTRACT: The three-dimensional configuration of the chromatin architecture is known to be crucial for alterations in the transcriptional network; however, the underlying mechanisms of epigenetic control of senescence-related gene expression by modulating the chromatin architecture remain unknown. Here, we demonstrate frequent chromosomal compartment switching during mouse embryonic fibroblasts (MEFs) replicative senescence as characterized by senescence-inactivated (SIAEs) and -activated enhancers (SAEs) in topologically associated domains (TADs). Mechanistically, SAEs are closely correlated with senescence-associated secretory phenotype (SASP) genes, which are a key transcriptional feature of an aging microenvironment that contributes to tumor progression, aging acceleration, and immunoinflammator

SUBMITTER: Guan Y 

PROVIDER: S-EPMC7641768 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature