Skip to main content
SpringerLink
Log in

Coarse Graining of a Giant Molecular System: The Chromatin Fiber

  • Protocol
  • First Online:
Biomolecular Simulations

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2022))

Abstract

The chromatin fiber is a complex polymer whose conformational properties are quite important to regulate gene transcription. One cannot but resort to coarse-grained models to describe the structure and the dynamics of this system on the length scale of the cellular nucleus. Bulk biological data can be used within the framework of the principle of maximum entropy to generate a realistic interaction potential that can be used to sample the equilibrium state of the fiber. The analysis of the structure and of the dynamics of the fiber can be correlated with its biological function, thus providing interesting results about transcriptional regulation.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 199.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 299.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Bonev B, Cavalli G (2016) Organization and function of the 3D genome. Nat Rev Genet 17:661–678

    Article  CAS  Google Scholar 

  2. Robinson PJJ, Fairall L, Huynh VAT et al (2006) EM measurements define the dimensions of the “30-nm” chromatin fiber: evidence for a compact, interdigitated structure. Proc Natl Acad Sci U S A 103:6506–6511

    Article  CAS  Google Scholar 

  3. Ou HD, Phan S, Deerinck TJ et al (2017) ChromEMT: visualizing 3D chromatin structure and compaction in interphase and mitotic cells. Science 357:eaag0025

    Article  Google Scholar 

  4. Bystricky K, Heun P, Gehlen L et al (2004) Long-range compaction and flexibility of interphase chromatin in budding yeast analyzed by high-resolution imaging techniques. Proc Natl Acad Sci U S A 101:16495–16500

    Article  CAS  Google Scholar 

  5. Cremer T, Cremer C (2001) Chromosome territories, nuclear architecture and gene regulation in mammalian cells. Nat Rev Genet 2:292–301

    Article  CAS  Google Scholar 

  6. Spitz F (2016) Gene regulation at a distance: from remote enhancers to 3D regulatory ensembles. Semin Cell Dev Biol 57:57–67

    Article  CAS  Google Scholar 

  7. Ozer G, Luque A, Schlick T (2015) The chromatin fiber: multiscale problems and approaches. Curr Opin Struct Biol 31:124–139

    Article  CAS  Google Scholar 

  8. Dans PD, Walther J, Gómez H et al (2016) Multiscale simulation of DNA. Curr Opin Struct Biol 37:29–45

    Article  CAS  Google Scholar 

  9. Nora EP, Goloborodko A, Valton AL et al (2017) Targeted degradation of CTCF decouples local insulation of chromosome domains from genomic compartmentalization. Cell 169:930–944

    Article  CAS  Google Scholar 

  10. Merkenschlager M, Nora EP (2016) CTCF and cohesin in genome folding and transcriptional gene regulation. Annu Rev Genomics Hum Genet 17:17–43

    Article  CAS  Google Scholar 

  11. Schwarzer W, Abdennur N, Goloborodko A et al (2017) Two independent modes of chromatin organization revealed by cohesin removal. Nature 152:1270

    Google Scholar 

  12. Rao S, Huang S-C, Hilaire BGS et al (2017) Cohesin loss eliminates all loop domains, leading to links among superenhancers and downregulation of nearby genes. Cell 171:305–320

    Article  CAS  Google Scholar 

  13. 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

    Article  CAS  Google Scholar 

  14. Di Stefano M, Rosa A, Belcastro V et al (2013) Colocalization of coregulated genes: a steered molecular dynamics study of human chromosome 19. PLoS Comput Biol 9:e1003019

    Article  Google Scholar 

  15. Nazarov LI, Tamm MV, Avetisov VA et al (2015) A statistical model of intra-chromosome contact maps. Soft Matter 11:1019–1025

    Article  CAS  Google Scholar 

  16. Shukron O, Holcman D (2017) Transient chromatin properties revealed by polymer models and stochastic simulations constructed from chromosomal capture data. PLoS Comput Biol 13:e1005469

    Article  Google Scholar 

  17. Tark-Dame M, Jerabek H, Manders EMM et al (2014) Depletion of the chromatin looping proteins CTCF and cohesin causes chromatin compaction: insight into chromatin folding by polymer modelling. PLoS Comput Biol 10:e1003877

    Article  Google Scholar 

  18. Barbieri M, Chotalia M, Fraser J et al (2012) Complexity of chromatin folding is captured by the strings and binders switch model. Proc Natl Acad Sci U S A 109:16173–16178

    Article  CAS  Google Scholar 

  19. Johnson J, Brackley CA, Cook PR et al (2015) A simple model for DNA bridging proteins and bacterial or human genomes: bridging-induced attraction and genome compaction. J Phys Condens Matter 27:064119

    Article  CAS  Google Scholar 

  20. Brackley CA, Johnson J, Kelly S et al (2016) Simulated binding of transcription factors to active and inactive regions folds human chromosomes into loops, rosettes and topological domains. Nucleic Acids Res 44:3503–3512

    Article  CAS  Google Scholar 

  21. Marenduzzo D (2016) Predicting the three-dimensional folding of cis-regulatory regions in mammalian genomes using bioinformatic data and polymer models. Genome Biol 17:1–16

    Article  Google Scholar 

  22. Barbieri M, Xie SQ, Torlai Triglia E et al (2017) Active and poised promoter states drive folding of the extended HoxB locus in mouse embryonic stem cells. Nat Struct Mol Biol 24:515–524

    Article  CAS  Google Scholar 

  23. Fudenberg G, Imakaev M, Lu C et al (2016) Formation of chromosomal domains by loop extrusion. Cell Rep 15:2038–2049

    Article  CAS  Google Scholar 

  24. Goloborodko A, Marko JF, Mirny LA (2016) Chromosome compaction by active loop extrusion. Biophys J 110:2162–2168

    Article  CAS  Google Scholar 

  25. Brackley CA, Johnson J, Michieletto D et al (2017) Nonequilibrium chromosome looping via molecular slip links. Phys Rev Lett 119:138101

    Article  CAS  Google Scholar 

  26. Benedetti F, Dorier J, Burnier Y et al (2013) Models that include supercoiling of topological domains reproduce several known features of interphase chromosomes. Nucleic Acids Res 42:2848–2855

    Article  Google Scholar 

  27. Benedetti F, Racko D, Dorier J et al (2017) Transcription-induced supercoiling explains formation of self-interacting chromatin domains in S. pombe. Nucleic Acids Res 45:9850–9859

    Article  CAS  Google Scholar 

  28. Rosa A, Everaers R (2008) Structure and dynamics of interphase chromosomes. PLoS Comput Biol 4:e1000153

    Article  Google Scholar 

  29. Tiana G, Amitai A, Pollex T et al (2016) Structural fluctuations of the chromatin fiber within topologically associating domains. Biophys J 110:1234–1245

    Article  CAS  Google Scholar 

  30. Jaynes ET (1957) Information theory and statistical mechanics. Phys Rev 106:620–630

    Article  Google Scholar 

  31. Pitera JW, Chodera JD (2012) On the use of experimental observations to bias simulated ensembles. J Chem Theory Comput 8:3445–3451

    Article  CAS  Google Scholar 

  32. Roux B, Weare J (2013) On the statistical equivalence of restrained-ensemble simulations with the maximum entropy method. J Chem Phys 138:084107–084109

    Article  Google Scholar 

  33. Cavalli A, Camilloni C, Vendruscolo M (2013) Molecular dynamics simulations with replica-averaged structural restraints generate structural ensembles according to the maximum entropy principle. J Chem Phys 138:094112

    Article  Google Scholar 

  34. White AD, Voth GA (2014) Efficient and minimal method to bias molecular simulations with experimental data. J Chem Theory Comput 10:3023–3030

    Article  CAS  Google Scholar 

  35. Cesari A, Gil-Ley A, Bussi G (2016) Combining simulations and solution experiments as a paradigm for RNA force field refinement. J Chem Theory Comput 12:6192–6200

    Article  CAS  Google Scholar 

  36. Norgaard AB, Ferkinghoff-Borg J, Lindorff-Larsen K (2008) Experimental parameterization of an energy function for the simulation of unfolded proteins. Biophys J 94:182–192

    Article  CAS  Google Scholar 

  37. Dekker J, Rippe K, Dekker M et al (2002) Capturing chromosome conformation. Science 295:1306–1311

    Article  CAS  Google Scholar 

  38. Dostie J, Richmond TA, Arnaout RA et al (2006) Chromosome conformation capture carbon copy (5C): a massively parallel solution for mapping interactions between genomic elements. Genome Res 16:1299–1309

    Article  CAS  Google Scholar 

  39. Lieberman-Aiden E, van Berkum NL, Williams L et al (2009) Comprehensive mapping of long-range interactions reveals folding principles of the human genome. Science 326:289–293

    Article  CAS  Google Scholar 

  40. Giorgetti L, Heard E (2016) Closing the loop: 3C versus DNA FISH. Genome Biol 17:215

    Article  Google Scholar 

  41. Nora EP, Lajoie BR, Schulz EG et al (2012) Spatial partitioning of the regulatory landscape of the X-inactivation centre. Nature 485:381–385

    Article  CAS  Google Scholar 

  42. Dixon JR, Selvaraj S, Yue F et al (2012) Topological domains in mammalian genomes identified by analysis of chromatin interactions. Nature 485:376–380

    Article  CAS  Google Scholar 

  43. Sexton T, Yaffe E, Kenigsberg E et al (2012) Three-dimensional folding and functional organization principles of the Drosophila genome. Cell 148:458–472

    Article  CAS  Google Scholar 

  44. Zhan Y, Mariani L, Barozzi I et al (2017) Reciprocal insulation analysis of Hi-C data shows that TADs represent a fu nctionally but not structurally privileged scale in the hierarchical folding of chromosomes. Genome Res 27:479–490

    Article  CAS  Google Scholar 

  45. Giorgetti L, Galupa R, Nora EP et al (2014) Predictive polymer modeling reveals coupled fluctuations in chromosome conformation and transcription. Cell 157:950–963

    Article  CAS  Google Scholar 

  46. Zhan Y, Giorgetti L, Tiana G (2017) Modelling genome-wide topological associating domains in mouse embryonic stem cells. Chromosom Res 25:5–14

    Article  CAS  Google Scholar 

  47. Tiana G, Sutto L, Broglia RA (2007) Use of the metropolis algorithm to simulate the dynamics of protein chains. Physica A 380:241–249

    Article  CAS  Google Scholar 

  48. Tiana G, Villa F, Zhan Y et al (2014) MonteGrappa: an iterative Monte Carlo program to optimize biomolecular potentials in simplified models. Comput Phys Commun 186:93–104

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Physics and Center for Complexity and Biosystems, Università Degli Studi di Milano and INFN, Milan, Italy

    Guido Tiana

  2. Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland

    Luca Giorgetti

Authors
  1. Guido Tiana
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Luca Giorgetti
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Luca Giorgetti .

Editor information

Editors and Affiliations

  1. Structural Bioinformatics Unit, Institut Pasteur, CNRS UMR 3528, Paris, France

    Massimiliano Bonomi

  2. Dipartimento di Bioscienze, Università degli Studi di Milano, Milano, Italy

    Carlo Camilloni

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Science+Business Media, LLC, part of Springer Nature

About this protocol

Check for updates. Verify currency and authenticity via CrossMark

Cite this protocol

Tiana, G., Giorgetti, L. (2019). Coarse Graining of a Giant Molecular System: The Chromatin Fiber. In: Bonomi, M., Camilloni, C. (eds) Biomolecular Simulations. Methods in Molecular Biology, vol 2022. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-9608-7_17

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-9608-7_17

  • Published:

  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-4939-9607-0

  • Online ISBN: 978-1-4939-9608-7

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation