Involvement of Condensin in Cellular Senescence through Gene Regulation and Compartmental Reorganization

Cellular senescence is a state of stable cell growth arrest induced by various stimuli such as oncogene expression and telomere shortening, referred to as oncogene-induced senescence (OIS) and replicative senescence (RS), respectively. Senescence is accompanied not only by global transcriptional alterations but also by 3D genome reorganization. Here we demonstrate that the human condensin II complex participates in cellular senescence via gene regulation and reorganization of euchromatic A and heterochromatic B chromatin compartments. OIS and RS are accompanied by A-to-B and B-to-A compartmental transitions, the latter of which occur more frequently and account for 15% of the human genome. Mechanistically, condensin is enriched at A compartments, especially at gene promoters and typical/super enhancers, and implicated in the B-to-A transitions. Genes present at B-to-A-switching regions tend to be up-regulated. The full activation of senescence genes (SASP genes and p53 targets) requires condensin; its depletion impairs senescence markers such as the activity of senescence-associated beta-galactosidase (SA-beta-gal) and senescence-associated heterochromatic foci (SAHF). This study describes that condensin reinforces euchromatic A compartments and is required for optimal expression of senescence genes, thereby contributing to the establishment and maintenance of the senescent state.