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Chromatin epigenomic domain folding: size matters

1 Sorbonne Universités UPMC Univ. Paris 06 UMR 7600 LPTMC F-75005 Paris France;
2 CNRS UMR 7600 LPTMC F-75005 Paris France;
3 CNRS GDR 3536

Special Issues: Chromatin and Epigenetics

In eukaryotes, chromatin is coated with epigenetic marks which induce differential gene expression profiles and eventually lead to different cellular phenotypes. One of the challenges of contemporary cell biology is to relate the wealth of epigenomic data with the observed physical properties of chromatin. In this study, we present a polymer physics framework that takes into account the sizes of epigenomic domains. We build a model of chromatin as a block copolymer made of domains with various sizes. This model produces a rich set of conformations which is well explained by finite-size scaling analysis of the coil-globule transition of epigenomic domains. Our results suggest that size-dependent folding of epigenomic domains may be a crucial physical mechanism able to provide chromatin with tissue-specific folding states, these being associated with differential gene expression.
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Keywords epigenetics; chromatin; coil-globule transition; polymer physics; finite-size effects; langevin dynamics

Citation: Bertrand R. Caré, Pierre-Emmanuel Emeriau, Ruggero Cortini, Jean-Marc Victor. Chromatin epigenomic domain folding: size matters. AIMS Biophysics, 2015, 2(4): 517-530. doi: 10.3934/biophy.2015.4.517


  • 1. Zentner GE, Henikoff S (2013) Regulation of nucleosome dynamics by histone modifications. Nat Struct Mol Biol 20: 259-266.    
  • 2. Ho JWK, Jung YL, Liu T, et al. (2014) Comparative analysis of metazoan chromatin organization. Nature 512: 449-452.    
  • 3. Amin V, Harris RA, Onuchic V, et al. (2015) Epigenomic footprints across 111 reference epigenomes reveal tissue-specific epigenetic regulation of lincRNAs. Nat Commun 6: 6370.    
  • 4. Roadmap Epigenomics Consortium, Kundaje A, Meuleman W, Ernst J, et al. (2015) Integrative analysis of 111 reference human epigenomes. Nature 518: 317-330. Available from: http://www.nature.com/nature/journal/v518/n7539/abs/nature14248.html.    
  • 5. Cantone I, Fisher AG (2013) Epigenetic programming and reprogramming during development. Nat Struct Mol Biol 20: 282-289.    
  • 6. Zhu J, Adli M, Zou JY, et al. (2013) Genome-wide chromatin state transitions associated with developmental and environmental cues. Cell 152: 642-654.    
  • 7. Chen T, Dent SYR (2014) Chromatin modifiers and remodellers: regulators of cellular differentiation. Nat Rev Genet 15: 93-106.
  • 8. Lieberman-Aiden E, van Berkum NL, Williams L, et al. (2009) Comprehensive mapping of longrange interactions reveals folding principles of the human genome. Science (New York NY) 326: 289-293.    
  • 9. Rao SSP, Huntley MH, Durand NC, et al. (2014) A 3d map of the human genome at kilobase resolution reveals principles of chromatin looping. Cell 159: 1665-1680.    
  • 10. Dixon JR, Selvaraj S, Yue F, et al. (2012) Topological domains in mammalian genomes identified by analysis of chromatin interactions. Nature 485:376-380.    
  • 11. Sexton T, Yaffe E, Kenigsberg E, et al. (2012) Three-dimensional folding and functional organization principles of the drosophila genome. Cell 148: 458-472.    
  • 12. Nora EP, Lajoie BR, Schulz EG, et al. (2012) Spatial partitioning of the regulatory landscape of the x-inactivation centre. Nature 485: 381-385.    
  • 13. Palstra RJ, Tolhuis B, Splinter E, et al. (2003) The beta-globin nuclear compartment in development and erythroid differentiation. Nat Genet 35: 190-194.    
  • 14. Zhang Y, Wong CH, Birnbaum RY, et al. (2013) Chromatin connectivity maps reveal dynamic promoter-enhancer long-range associations. Nature 504: 306-310.    
  • 15. Le Dily F, BaùD, Pohl A, et al. (2014) Distinct structural transitions of chromatin topological domains correlate with coordinated hormone-induced gene regulation. Genes Dev 28: 2151-2162.    
  • 16. Li G, Ruan X, Auerbach RK, et al. (2012) Extensive promoter-centered chromatin interactions provide a topological basis for transcription regulation. Cell 148: 84-98. Available from: http: //www.cell.com/article/S0092867411015170/abstract.    
  • 17. Filion GJ, van Bemmel JG, Braunschweig U, et al. (2010) Systematic protein location mapping reveals five principal chromatin types in drosophila cells. Cell 143: 212-224.    
  • 18. Ernst J, Kheradpour P, Mikkelsen TS, et al. (2011) Mapping and analysis of chromatin state dynamics in nine human cell types. Nature 473: 43-49.    
  • 19. Boulé JB, Mozziconacci J, Lavelle C (2015) The polymorphisms of the chromatin fiber. J Phys Condens Matter 27: 033101. Available from: http://iopscience.iop.org/0953-8984/27/3/033101.    
  • 20. Barbieri M, Fraser J, Lavitas LM, et al. (2013) A polymer model explains the complexity of largescale chromatin folding. Nucleus Austin Tex 4: 267-273.
  • 21. Nicodemi M, Pombo A (2014) Models of chromosome structure. Curr Opin Cell Biol 28: 90-95.    
  • 22. Giorgetti L, Galupa R, Nora EP, et al. (2014) Predictive polymer modeling reveals coupled fluctuations in chromosome conformation and transcription. Cell 157: 950-963.    
  • 23. Jost D, Carrivain P, Cavalli G, et al. (2014) Modeling epigenome folding: formation and dynamics of topologically associated chromatin domains. Nucleic Acids Res 42: 9553-9561.    
  • 24. Caré BR, Carrivain P, Forné T, et al. (2014) Finite-size conformational transitions: A unifying concept underlying chromosome dynamics. Commun Theor Phys 62: 607. Available from: http://iopscience.iop.org/0253-6102/62/4/18.    
  • 25. Gennes PG (1979) Scaling Concepts in Polymer Physics, Cornell University Press, Ithaca, NY.
  • 26. Imbert JB, Lesne A, Victor JM (1997) Distribution of the order parameter of the coil-globule transition. Phys Rev E 56: 5630-5647. Available from: http://link.aps.org/doi/10.1103/PhysRevE.56.5630.    
  • 27. Ponmurugan M, Narasimhan SL, Krishna PSR, et al. (2007) Coil-globule transition of a single short polymer chain: an exact enumeration study. J Chem Phys 126: 144906.    
  • 28. Baumg C, Srtner A (1980) Statics and dynamics of the freely jointed polymer chain with lennardb jones interaction. J Chem Phys 72: 871-879. Available from: http://scitation.aip.org/content/aip/journal/jcp/72/2/10.1063/1.439242.    
  • 29. Hsu HP (2014) Monte carlo simulations of lattice models for single polymer systems. J Chem Phys 141: 164903. Available from: http://scitation.aip.org/content/aip/journal/jcp/141/16/10.1063/1.4899258.    
  • 30. Yoshikawa K, Matsuzawa Y (1995) Discrete phase transition of giant DNA dynamics of globule formation from a single molecular chain. Physica D: Nonlinear Phenomena 84: 220-227. Available from: http://www.sciencedirect.com/science/article/pii/0167278995000205.    
  • 31. Caré BR (2013) Cgmdode : Coarse-grained macromolecular dynamics with open dynamics engine. Available from: https://bitbucket.org/bcare/cgmdode-hg.
  • 32. Bussi G, Parrinello M (2008) Stochastic thermostats: comparison of local and global schemes. Comput Phys Commun 179: 26-29. Available from: http://www.sciencedirect.com/ science/article/pii/S0010465508000106.    
  • 33. Carrivain P, Barbi M, Victor JM (2014) In silico single-molecule manipulation of DNA with rigid body dynamics, PLoS Comput Biol 10: e1003456. http://www.ncbi.nlm.nih.gov/pmc/ articles/PMC3930497/.
  • 34. Cortini R, Caré BR, Victor JM, et al. (2015) Theory and simulations of toroidal and rod-like structures in single-molecule DNA condensation. J Chem Phys 142: 105102. Available from: http://scitation.aip.org/content/aip/journal/jcp/142/10/10.1063/1.4914513.    
  • 35. Maeshima K, Imai R, Tamura S, et al. (2014) Chromatin as dynamic 10-nm fibers. Chromosoma 123: (2014), 225-237.
  • 36. Fierz B (2014) Synthetic chromatin approaches to probe the writing and erasing of histone modifications. Chem Med Chem 9: 495-504.    
  • 37. Dodd IB, Sneppen K (2011) Barriers and silencers: a theoretical toolkit for control and containment of nucleosome-based epigenetic states. J Mol Biol 414: 624-637.    
  • 38. Dayarian A, Sengupta AM (2013) Titration and hysteresis in epigenetic chromatin silencing. Phys Biol 10: 036005.    
  • 39. Nagano T, Lubling Y, Stevens TJ, et al. (2013) Single-cell hi-c reveals cell-to-cell variability in chromosome structure. Nature 502: 59-64. Available from: http://www.nature.com/nature/journal/v502/n7469/full/nature12593.html.    


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Copyright Info: 2015, Jean-Marc Victor, et al., licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution Licese (http://creativecommons.org/licenses/by/4.0)

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