Lamin B1 depletion in senescent cells triggers large-scale changes in gene expression and the chromatin landscape

Senescence is a stable proliferation arrest, associated with an altered secretory pathway, thought to promote tumor suppression and tissue aging. While chromatin regulation and lamin B1 down-regulation have been implicated as senescence effectors, functional interactions between them are poorly understood. We compared genome-wide Lys4 trimethylation on histone H3 (H3K4me3) and H3K27me3 distributions between proliferating and senescent human cells and found dramatic differences in senescence, including large-scale domains of H3K4me3- and H3K27me3-enriched "mesas" and H3K27me3-depleted "canyons." Mesas form at lamin B1-associated domains (LADs) in replicative senescence and oncogene-induced senescence and…

• UO
  University of Pennsylvania
• CR
  Cancer Research UK
• NI
  National Institutes of Health

  Award: P01AG031862
• BI
  Beatson Institute for Cancer Research
• NI
  National Institute on Aging

  Award: P01AG031862