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

Overview

Journal Nat Commun

Specialty Biology

Date 2019 Dec 14

PMID 31831736

Citations 28

Authors

Osamu Iwasaki

Hideki Tanizawa

Kyoung-Dong Kim

Andrew Kossenkov

Timothy Nacarelli

Sanki Tashiro

Sonali Majumdar

Louise C Showe

Rugang Zhang

Ken-Ichi Noma

Affiliations

Soon will be listed here.

Abstract

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.

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References

Rai T, Cole J, Nelson D, Dikovskaya D, Faller W, Vizioli M . HIRA orchestrates a dynamic chromatin landscape in senescence and is required for suppression of neoplasia. Genes Dev. 2014; 28(24):2712-25. PMC: 4265675. DOI: 10.1101/gad.247528.114. View

Chandra T, Ewels P, Schoenfelder S, Furlan-Magaril M, Wingett S, Kirschner K . Global reorganization of the nuclear landscape in senescent cells. Cell Rep. 2015; 10(4):471-83. PMC: 4542308. DOI: 10.1016/j.celrep.2014.12.055. View

Tanaka A, Tanizawa H, Sriswasdi S, Iwasaki O, Chatterjee A, Speicher D . Epigenetic regulation of condensin-mediated genome organization during the cell cycle and upon DNA damage through histone H3 lysine 56 acetylation. Mol Cell. 2012; 48(4):532-46. PMC: 3513591. DOI: 10.1016/j.molcel.2012.09.011. View

Dixon J, Selvaraj S, Yue F, Kim A, Li Y, Shen Y . Topological domains in mammalian genomes identified by analysis of chromatin interactions. Nature. 2012; 485(7398):376-80. PMC: 3356448. DOI: 10.1038/nature11082. View

Tang Z, Luo O, Li X, Zheng M, Zhu J, Szalaj P . CTCF-Mediated Human 3D Genome Architecture Reveals Chromatin Topology for Transcription. Cell. 2015; 163(7):1611-27. PMC: 4734140. DOI: 10.1016/j.cell.2015.11.024. View

Uhlmann F . SMC complexes: from DNA to chromosomes. Nat Rev Mol Cell Biol. 2016; 17(7):399-412. DOI: 10.1038/nrm.2016.30. View

Haeusler R, Pratt-Hyatt M, Good P, Gipson T, Engelke D . Clustering of yeast tRNA genes is mediated by specific association of condensin with tRNA gene transcription complexes. Genes Dev. 2008; 22(16):2204-14. PMC: 2518813. DOI: 10.1101/gad.1675908. View

Yokoyama Y, Zhu H, Zhang R, Noma K . A novel role for the condensin II complex in cellular senescence. Cell Cycle. 2015; 14(13):2160-70. PMC: 4613835. DOI: 10.1080/15384101.2015.1049778. View

Lieberman-Aiden E, van Berkum N, Williams L, Imakaev M, Ragoczy T, Telling A . Comprehensive mapping of long-range interactions reveals folding principles of the human genome. Science. 2009; 326(5950):289-93. PMC: 2858594. DOI: 10.1126/science.1181369. View

10.

Coppe J, Desprez P, Krtolica A, Campisi J . The senescence-associated secretory phenotype: the dark side of tumor suppression. Annu Rev Pathol. 2010; 5:99-118. PMC: 4166495. DOI: 10.1146/annurev-pathol-121808-102144. View

11.

Li L, Lyu X, Hou C, Takenaka N, Nguyen H, Ong C . Widespread rearrangement of 3D chromatin organization underlies polycomb-mediated stress-induced silencing. Mol Cell. 2015; 58(2):216-31. PMC: 4402144. DOI: 10.1016/j.molcel.2015.02.023. View

12.

Rao S, Huang S, St Hilaire B, Engreitz J, Perez E, Kieffer-Kwon K . Cohesin Loss Eliminates All Loop Domains. Cell. 2017; 171(2):305-320.e24. PMC: 5846482. DOI: 10.1016/j.cell.2017.09.026. View

13.

Hocquet C, Robellet X, Modolo L, Sun X, Burny C, Cuylen-Haering S . Condensin controls cellular RNA levels through the accurate segregation of chromosomes instead of directly regulating transcription. Elife. 2018; 7. PMC: 6173581. DOI: 10.7554/eLife.38517. View

14.

Aird K, Iwasaki O, Kossenkov A, Tanizawa H, Fatkhutdinov N, Bitler B . HMGB2 orchestrates the chromatin landscape of senescence-associated secretory phenotype gene loci. J Cell Biol. 2016; 215(3):325-334. PMC: 5100296. DOI: 10.1083/jcb.201608026. View

15.

Rao S, Huntley M, Durand N, Stamenova E, Bochkov I, Robinson J . A 3D map of the human genome at kilobase resolution reveals principles of chromatin looping. Cell. 2014; 159(7):1665-80. PMC: 5635824. DOI: 10.1016/j.cell.2014.11.021. View

16.

Durand N, Shamim M, Machol I, Rao S, Huntley M, Lander E . Juicer Provides a One-Click System for Analyzing Loop-Resolution Hi-C Experiments. Cell Syst. 2016; 3(1):95-8. PMC: 5846465. DOI: 10.1016/j.cels.2016.07.002. View

17.

Kagey M, Newman J, Bilodeau S, Zhan Y, Orlando D, van Berkum N . Mediator and cohesin connect gene expression and chromatin architecture. Nature. 2010; 467(7314):430-5. PMC: 2953795. DOI: 10.1038/nature09380. View

18.

Criscione S, De Cecco M, Siranosian B, Zhang Y, Kreiling J, Sedivy J . Reorganization of chromosome architecture in replicative cellular senescence. Sci Adv. 2016; 2(2):e1500882. PMC: 4788486. DOI: 10.1126/sciadv.1500882. View

19.

Nakazawa N, Sajiki K, Xu X, Villar-Briones A, Arakawa O, Yanagida M . RNA pol II transcript abundance controls condensin accumulation at mitotically up-regulated and heat-shock-inducible genes in fission yeast. Genes Cells. 2015; 20(6):481-99. PMC: 4471619. DOI: 10.1111/gtc.12239. View

20.

Teytelman L, Thurtle D, Rine J, van Oudenaarden A . Highly expressed loci are vulnerable to misleading ChIP localization of multiple unrelated proteins. Proc Natl Acad Sci U S A. 2013; 110(46):18602-7. PMC: 3831989. DOI: 10.1073/pnas.1316064110. View