Involvement of condensin in cellular senescence through gene regulation and compartmental reorganization

• Published in: Nature communications Vol. 10; no. 1; pp. 5688 - 20
• Main Authors: Iwasaki, Osamu, Tanizawa, Hideki, Kim, Kyoung-Dong, Kossenkov, Andrew, Nacarelli, Timothy, Tashiro, Sanki, Majumdar, Sonali, Showe, Louise C., Zhang, Rugang, Noma, Ken-ichi
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 12.12.2019; Nature Publishing Group; Nature Portfolio
• Subjects: 38; 38/15; 38/32; 38/89; 45; 45/23; 631/208/212; 631/337/100/101; 631/337/386; 631/80/509; Adenosine Triphosphatases - metabolism; Adenosine Triphosphatases - pharmacology; Cell Cycle Proteins - genetics; Cell Line; Cell proliferation; Cellular Senescence - genetics; Cellular Senescence - physiology; Chromatin; Compartments; Condensin; DNA-Binding Proteins - metabolism; DNA-Binding Proteins - pharmacology; Gene expression; Gene Expression Profiling; Gene Expression Regulation, Neoplastic - drug effects; Gene Knockdown Techniques; Gene regulation; Genomes; Genomics; Humanities and Social Sciences; Humans; multidisciplinary; Multiprotein Complexes - metabolism; Multiprotein Complexes - pharmacology; Nuclear Proteins - genetics; Oncogenes; Promoter Regions, Genetic; Science; Science (multidisciplinary); Senescence; Telomere Shortening; Tumor Suppressor Protein p53 - genetics
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-019-13604-5

Senescence is induced by various stimuli such as oncogene expression and telomere shortening, referred to as oncogene-induced senescence (OIS) and replicative senescence (RS), respectively, and accompanied by global transcriptional alterations and 3D genome reorganization. Here, we demonstrate that the human condensin II complex participates in senescence via gene regulation and reorganization of euchromatic A and heterochromatic B compartments. Both OIS and RS are accompanied by A-to-B and B-to-A compartmental transitions, the latter of which occur more frequently and are undergone by 14% (430 Mb) of the human genome. Mechanistically, condensin is enriched in A compartments and implicated in B-to-A transitions. The full activation of senescence genes (SASP genes and p53 targets) requires condensin; its depletion impairs senescence markers. This study describes that condensin reinforces euchromatic A compartments and promotes B-to-A transitions, both of which are coupled to optimal expression of senescence genes, thereby allowing condensin to contribute to senescent processes. Cell senescence involves stable arrest of cell proliferation and changes in gene expression and 3D genome reorganization. Here, the authors show that human condensin II complex participates in reorganization of the chromatin compartments, primarily through switching from heterochromatic B to euchromatic A compartments.