Current Genetics

, Volume 65, Issue 5, pp 1145–1151 | Cite as

Unraveling quiescence-specific repressive chromatin domains

  • Sarah G. Swygert
  • Toshio TsukiyamaEmail author


Quiescence is a highly conserved inactive life stage in which the cell reversibly exits the cell cycle in response to external cues. Quiescence is essential for diverse processes such as the maintenance of adult stem cell stores, stress resistance, and longevity, and its misregulation has been implicated in cancer. Although the non-cycling nature of quiescent cells has made obtaining sufficient quantities of quiescent cells for study difficult, the development of a Saccharomyces cerevisiae model of quiescence has recently enabled detailed investigation into mechanisms underlying the quiescent state. Like their metazoan counterparts, quiescent budding yeast exhibit widespread transcriptional silencing and dramatic chromatin condensation. We have recently found that the structural maintenance of chromosomes (SMC) complex condensin binds throughout the quiescent budding yeast genome and induces the formation of large chromatin loop domains. In the absence of condensin, quiescent cell chromatin is decondensed and transcription is de-repressed. Here, we briefly discuss our findings in the larger context of the genome organization field.


Quiescence Condensin CIDs TADs Chromatin compaction Cohesin Micro-C XL 



S.G.S. has been supported by Grants F32GM120962 from NIGMS and T32CA009657 from NCI, and T.T. and S.G.S. were supported by NIGMS R01GM111428.


  1. Allen C, Buttner S, Aragon AD, Thomas JA, Meirelles O, Jaetao JE, Benn D, Ruby SW, Veenhuis M, Madeo F et al (2006) Isolation of quiescent and nonquiescent cells from yeast stationary-phase cultures. J Cell Biol 174:89–100CrossRefGoogle Scholar
  2. Aragon AD, Quinones GA, Thomas EV, Roy S, Werner-Washburne M (2006) Release of extraction-resistant mRNA in stationary phase Saccharomyces cerevisiae produces a massive increase in transcript abundance in response to stress. Genome Biol 7:R9CrossRefGoogle Scholar
  3. Bulger M, Groudine M (2011) Functional and mechanistic diversity of distal transcription enhancers. Cell 144:327–339CrossRefGoogle Scholar
  4. Busslinger GA, Stocsits RR, van der Lelij P, Axelsson E, Tedeschi A, Galjart N, Peters JM (2017) Cohesin is positioned in mammalian genomes by transcription, CTCF and Wapl. Nature 544:503–507CrossRefGoogle Scholar
  5. D’Ambrosio C, Schmidt CK, Katou Y, Kelly G, Itoh T, Shirahige K, Uhlmann F (2008) Identification of cis-acting sites for condensin loading onto budding yeast chromosomes. Genes Dev 22:2215–2227CrossRefGoogle Scholar
  6. De Virgilio C (2012) The essence of yeast quiescence. FEMS Microbiol Rev 36:306–339CrossRefGoogle Scholar
  7. de Wit E, Vos ES, Holwerda SJ, Valdes-Quezada C, Verstegen MJ, Teunissen H, Splinter E, Wijchers PJ, Krijger PH, de Laat W (2015) CTCF binding polarity determines chromatin looping. Mol Cell 60:676–684CrossRefGoogle Scholar
  8. Deng W, Lee J, Wang H, Miller J, Reik A, Gregory PD, Dean A, Blobel GA (2012) Controlling long-range genomic interactions at a native locus by targeted tethering of a looping factor. Cell 149:1233–1244CrossRefGoogle Scholar
  9. Dixon JR, Selvaraj S, Yue F, Kim A, Li Y, Shen Y, Hu M, Liu JS, Ren B (2012) Topological domains in mammalian genomes identified by analysis of chromatin interactions. Nature 485:376–380CrossRefGoogle Scholar
  10. Eeftens JM, Bisht S, Kerssemakers J, Kschonsak M, Haering CH, Dekker C (2017) Real-time detection of condensin-driven DNA compaction reveals a multistep binding mechanism. EMBO J 36:3448–3457CrossRefGoogle Scholar
  11. Estruch F (2000) Stress-controlled transcription factors, stress-induced genes and stress tolerance in budding yeast. FEMS Microbiol Rev 24:469–486CrossRefGoogle Scholar
  12. Evertts AG, Manning AL, Wang X, Dyson NJ, Garcia BA, Coller HA (2013) H4K20 methylation regulates quiescence and chromatin compaction. Mol Biol Cell 24:3025–3037CrossRefGoogle Scholar
  13. Fudenberg G, Abdennur N, Imakaev M, Goloborodko A, Mirny LA (2017) Emerging evidence of chromosome folding by loop extrusion. Cold Spring Harb Symp Quant Biol 82:45–55CrossRefGoogle Scholar
  14. Galdieri L, Mehrotra S, Yu S, Vancura A (2010) Transcriptional regulation in yeast during diauxic shift and stationary phase. OMICS 14:629–638CrossRefGoogle Scholar
  15. Ganji M, Shaltiel IA, Bisht S, Kim E, Kalichava A, Haering CH, Dekker C (2018) Real-time imaging of DNA loop extrusion by condensin. Science 360:102–105CrossRefGoogle Scholar
  16. Glynn EF, Megee PC, Yu HG, Mistrot C, Unal E, Koshland DE, DeRisi JL, Gerton JL (2004) Genome-wide mapping of the cohesin complex in the yeast Saccharomyces cerevisiae. PLoS Biol 2:E259CrossRefGoogle Scholar
  17. Gray JV, Petsko GA, Johnston GC, Ringe D, Singer RA, Werner-Washburne M (2004) “Sleeping beauty”: quiescence in Saccharomyces cerevisiae. Microbiol Mol Biol Rev 68:187–206CrossRefGoogle Scholar
  18. Gullerova M, Proudfoot NJ (2008) Cohesin complex promotes transcriptional termination between convergent genes in S. pombe. Cell 132:983–995CrossRefGoogle Scholar
  19. Haeusler RA, Pratt-Hyatt M, Good PD, Gipson TA, Engelke DR (2008) Clustering of yeast tRNA genes is mediated by specific association of condensin with tRNA gene transcription complexes. Genes Dev 22:2204–2214CrossRefGoogle Scholar
  20. Hansen AS, Cattoglio C, Darzacq X, Tjian R (2018) Recent evidence that TADs and chromatin loops are dynamic structures. Nucleus 9:20–32CrossRefGoogle Scholar
  21. Hassler M, Shaltiel IA, Haering CH (2018) Towards a unified model of SMC complex function. Curr Biol 28:R1266–R1281CrossRefGoogle Scholar
  22. Hocquet C, Robellet X, Modolo L, Sun XM, Burny C, Cuylen-Haering S, Toselli E, Clauder-Munster S, Steinmetz L, Haering CH et al (2018) Condensin controls cellular RNA levels through the accurate segregation of chromosomes instead of directly regulating transcription. Elife 7:e38517CrossRefGoogle Scholar
  23. Hsieh TH, Weiner A, Lajoie B, Dekker J, Friedman N, Rando OJ (2015) Mapping nucleosome resolution chromosome folding in yeast by micro-C. Cell 162:108–119CrossRefGoogle Scholar
  24. Hsieh TS, Fudenberg G, Goloborodko A, Rando OJ (2016) Micro-C XL: assaying chromosome conformation from the nucleosome to the entire genome. Nat Methods 13:1009–1011CrossRefGoogle Scholar
  25. Kakui Y, Uhlmann F (2018) SMC complexes orchestrate the mitotic chromatin interaction landscape. Curr Genet 64:335–339CrossRefGoogle Scholar
  26. Keenholtz RA, Dhanaraman T, Palou R, Yu J, D’Amours D, Marko JF (2017) Oligomerization and ATP stimulate condensin-mediated DNA compaction. Sci Rep 7:14279CrossRefGoogle Scholar
  27. Kim KD, Tanizawa H, Iwasaki O, Noma K (2016) Transcription factors mediate condensin recruitment and global chromosomal organization in fission yeast. Nat Genet 48:1242–1252CrossRefGoogle Scholar
  28. Kuang Z, Pinglay S, Ji H, Boeke JD (2017) Msn2/4 regulate expression of glycolytic enzymes and control transition from quiescence to growth. Elife 6:e29938CrossRefGoogle Scholar
  29. Kuang Z, Ji H, Boeke JD (2018) Stress response factors drive regrowth of quiescent cells. Curr Genet 64:807–810CrossRefGoogle Scholar
  30. Laporte D, Courtout F, Tollis S, Sagot I (2016) Quiescent Saccharomyces cerevisiae forms telomere hyperclusters at the nuclear membrane vicinity through a multifaceted mechanism involving Esc1, the Sir complex, and chromatin condensation. Mol Biol Cell 27:1875–1884CrossRefGoogle Scholar
  31. Lengronne A, Katou Y, Mori S, Yokobayashi S, Kelly GP, Itoh T, Watanabe Y, Shirahige K, Uhlmann F (2004) Cohesin relocation from sites of chromosomal loading to places of convergent transcription. Nature 430:573–578CrossRefGoogle Scholar
  32. Li L, Miles S, Breeden LL (2015) A genetic screen for saccharomyces cerevisiae mutants that fail to enter quiescence. G3 (Bethesda) 5:1783–1795CrossRefGoogle Scholar
  33. Litwin I, Wysocki R (2018) New insights into cohesin loading. Curr Genet 64:53–61CrossRefGoogle Scholar
  34. Lohr D, Ide G (1979) Comparison on the structure and transcriptional capability of growing phase and stationary yeast chromatin: a model for reversible gene activation. Nucleic Acids Res 6:1909–1927CrossRefGoogle Scholar
  35. Lupianez DG, Kraft K, Heinrich V, Krawitz P, Brancati F, Klopocki E, Horn D, Kayserili H, Opitz JM, Laxova R et al (2015) Disruptions of topological chromatin domains cause pathogenic rewiring of gene-enhancer interactions. Cell 161:1012–1025CrossRefGoogle Scholar
  36. Matityahu A, Onn I (2018) A new twist in the coil: functions of the coiled-coil domain of structural maintenance of chromosome (SMC) proteins. Curr Genet 64:109–116CrossRefGoogle Scholar
  37. Matsushima Y, Sakamoto N, Awazu A (2019) Insulator activities of nucleosome-excluding DNA sequences without bound chromatin looping proteins. J Phys Chem B 123:1035–1043CrossRefGoogle Scholar
  38. McKnight JN, Boerma JW, Breeden LL, Tsukiyama T (2015) Global promoter targeting of a conserved lysine deacetylase for transcriptional shutoff during quiescence entry. Mol Cell 59:732–743CrossRefGoogle Scholar
  39. Mizuguchi T, Fudenberg G, Mehta S, Belton JM, Taneja N, Folco HD, FitzGerald P, Dekker J, Mirny L, Barrowman J et al (2014) Cohesin-dependent globules and heterochromatin shape 3D genome architecture in S. pombe. Nature 516:432–435CrossRefGoogle Scholar
  40. Ngubo M, Kemp G, Patterton HG (2011) Nano-electrospray tandem mass spectrometric analysis of the acetylation state of histones H3 and H4 in stationary phase in Saccharomyces cerevisiae. BMC Biochem 12:34CrossRefGoogle Scholar
  41. Nora EP, Lajoie BR, Schulz EG, Giorgetti L, Okamoto I, Servant N, Piolot T, van Berkum NL, Meisig J, Sedat J et al (2012) Spatial partitioning of the regulatory landscape of the X-inactivation centre. Nature 485:381–385CrossRefGoogle Scholar
  42. Ocampo-Hafalla M, Munoz S, Samora CP, Uhlmann F (2016) Evidence for cohesin sliding along budding yeast chromosomes. Open Biol 6:15078CrossRefGoogle Scholar
  43. Paul MR, Markowitz TE, Hochwagen A, Ercan S (2018) Condensin depletion causes genome decompaction without altering the level of global gene expression in Saccharomyces cerevisiae. Genetics 210:331–344CrossRefGoogle Scholar
  44. Paul MR, Hochwagen A, Ercan S (2019) Condensin action and compaction. Curr Genet 65:407–415CrossRefGoogle Scholar
  45. Pinon R (1978) Folded chromosomes in non-cycling yeast cells: evidence for a characteristic g0 form. Chromosoma 67:263–274CrossRefGoogle Scholar
  46. Rao SS, Huntley MH, Durand NC, Stamenova EK, Bochkov ID, Robinson JT, Sanborn AL, Machol I, Omer AD, Lander ES et al (2014) A 3D map of the human genome at kilobase resolution reveals principles of chromatin looping. Cell 159:1665–1680CrossRefGoogle Scholar
  47. Rao SSP, Huang SC, St Hilaire BG, Engreitz JM, Perez EM, Kieffer-Kwon KR, Sanborn AL, Johnstone SE, Bascom GD, Bochkov ID et al (2017) Cohesin loss eliminates all loop domains. Cell 171(305–320):e324Google Scholar
  48. Rawlings JS, Gatzka M, Thomas PG, Ihle JN (2011) Chromatin condensation via the condensin II complex is required for peripheral T-cell quiescence. EMBO J 30:263–276CrossRefGoogle Scholar
  49. Robellet X, Vanoosthuyse V, Bernard P (2017) The loading of condensin in the context of chromatin. Curr Genet 63:577–589CrossRefGoogle Scholar
  50. Roche B, Arcangioli B, Martienssen R (2017) Transcriptional reprogramming in cellular quiescence. RNA Biol 14:843–853CrossRefGoogle Scholar
  51. Rutledge MT, Russo M, Belton JM, Dekker J, Broach JR (2015) The yeast genome undergoes significant topological reorganization in quiescence. Nucleic Acids Res 43:8299–8313CrossRefGoogle Scholar
  52. Sanborn AL, Rao SS, Huang SC, Durand NC, Huntley MH, Jewett AI, Bochkov ID, Chinnappan D, Cutkosky A, Li J et al (2015) Chromatin extrusion explains key features of loop and domain formation in wild-type and engineered genomes. Proc Natl Acad Sci USA 112:E6456–E6465CrossRefGoogle Scholar
  53. Sutani T, Sakata T, Nakato R, Masuda K, Ishibashi M, Yamashita D, Suzuki Y, Hirano T, Bando M, Shirahige K (2015) Condensin targets and reduces unwound DNA structures associated with transcription in mitotic chromosome condensation. Nat Commun 6:7815CrossRefGoogle Scholar
  54. Swygert SG, Kim S, Wu X, Fu T, Hsieh TH, Rando OJ, Eisenman RN, Shendure J, McKnight JN, Tsukiyama T (2019) Condensin-dependent chromatin compaction represses transcription globally during quiescence. Mol Cell 73(533–546):e534Google Scholar
  55. Tanizawa H, Kim KD, Iwasaki O, Noma KI (2017) Architectural alterations of the fission yeast genome during the cell cycle. Nat Struct Mol Biol 24:965–976CrossRefGoogle Scholar
  56. Terakawa T, Bisht S, Eeftens JM, Dekker C, Haering CH, Greene EC (2017) The condensin complex is a mechanochemical motor that translocates along DNA. Science 358:672–676CrossRefGoogle Scholar
  57. Toselli-Mollereau E, Robellet X, Fauque L, Lemaire S, Schiklenk C, Klein C, Hocquet C, Legros P, N’Guyen L, Mouillard L et al (2016) Nucleosome eviction in mitosis assists condensin loading and chromosome condensation. EMBO J 35:1565–1581CrossRefGoogle Scholar
  58. Wang X, Hughes AC, Brandao HB, Walker B, Lierz C, Cochran JC, Oakley MG, Kruse AC, Rudner DZ (2018) In vivo evidence for ATPase-dependent DNA translocation by the Bacillus subtilis SMC condensin complex. Mol Cell 71(841–847):e845Google Scholar
  59. Werner-Washburne M, Braun E, Johnston GC, Singer RA (1993) Stationary phase in the yeast Saccharomyces cerevisiae. Microbiol Rev 57:383–401Google Scholar
  60. Young CP, Hillyer C, Hokamp K, Fitzpatrick DJ, Konstantinov NK, Welty JS, Ness SA, Werner-Washburne M, Fleming AB, Osley MA (2017) Distinct histone methylation and transcription profiles are established during the development of cellular quiescence in yeast. BMC Genom 18:107CrossRefGoogle Scholar
  61. Yuen KC, Gerton JL (2018) Taking cohesin and condensin in context. PLoS Genet 14:e1007118CrossRefGoogle Scholar
  62. Yuen KC, Slaughter BD, Gerton JL (2017) Condensin II is anchored by TFIIIC and H3K4me3 in the mammalian genome and supports the expression of active dense gene clusters. Sci Adv 3:e1700191CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Basic Sciences DivisionFred Hutchinson Cancer Research CenterSeattleUSA

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