Due to recent advances in experimental and theoretical approaches, the dynamic three-dimensional organization (3D) of the nucleus has become a very active area of research in life sciences. We now understand that the linear genome is folded in ways that may modulate how genes are expressed during the basic functioning of cells. Importantly, it is now possible to build 3D models of how the genome folds within the nucleus and changes over time (4D). Because genome folding influences its function, this opens exciting new possibilities to broaden our understanding of the mechanisms that determine cell fate. However, the rapid evolution of methods and the increasing complexity of data can result in ambiguity and reproducibility challenges, which may hamper the progress of this field. Here, we describe such challenges ahead and provide guidelines to think about strategies for shared standardized validation of experimental 4D nucleome data sets and models.

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We thank the community of researchers around the EU 4DNucleome Initiative for their continuous support.

Author information


  1. Gene Regulation, Stem Cells and Cancer Program, CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain

    • Marc A. Marti-Renom
  2. Universitat Pompeu Fabra (UPF), Barcelona, Spain

    • Marc A. Marti-Renom
  3. ICREA, Barcelona, Spain

    • Marc A. Marti-Renom
  4. Institut Curie, PSL Research University, CNRS UMR3664, Paris, France

    • Genevieve Almouzni
  5. MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine at the University of Edinburgh, Edinburgh, UK

    • Wendy A. Bickmore
  6. Laboratoire de Biologie Molécualire Eucaryote (LBME), Centre de Biologie Intégrative (CBI), University of Toulouse, UPS, CNRS, Toulouse, France

    • Kerstin Bystricky
  7. Institute of Human Genetics, UMR 9002 of the CNRS and the University of Montpellier, Montpellier, France

    • Giacomo Cavalli
  8. Nuclear Dynamics Programme, The Babraham Institute, Cambridge, UK

    • Peter Fraser
  9. Department of Biological Science, Florida State University, Tallahassee, Florida, USA

    • Peter Fraser
  10. Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland

    • Susan M. Gasser
    •  & Luca Giorgetti
  11. University of Basel, Basel, Switzerland

    • Susan M. Gasser
  12. Institut Curie, PSL Research University, CNRS UMR3215, INSERM U934, Paris, France

    • Edith Heard
  13. Dipartimento di Fisica “E. Pancini”, Università di Napoli “Federico II”, INFN Sezione di Napoli, Naples, Italy

    • Mario Nicodemi
  14. Berlin Institute of Health, MDC-Berlin, Berlin, Germany

    • Mario Nicodemi
    •  & Ana Pombo
  15. Centre de Biochimie Structurale, CNRS UMR5048, INSERM U1054, Universite de Montpellier, Montpellier, France

    • Marcelo Nollmann
  16. Institute for Research in Biomedicine Barcelona (IRB), The Barcelona Institute of Science and Technology (BIST), Barcelona, Spain

    • Modesto Orozco
  17. Departament de Bioquimica i Biologia Molecular, Universitat de Barcelona, Barcelona, Spain

    • Modesto Orozco
  18. Epigenetic Regulation and Chromatin Architecture, Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine, Berlin, Germany

    • Ana Pombo
  19. Institute for Biology, Humboldt-Universitat zu Berlin, Berlin, Germany

    • Ana Pombo
  20. Institute of Epigenetics and Stem Cells (IES), Helmholtz Zentrum Munchen, München, Germany

    • Maria-Elena Torres-Padilla
  21. Faculty of Biology, Ludwig-Maximilians Universitat, München, Germany

    • Maria-Elena Torres-Padilla


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Correspondence to Marc A. Marti-Renom.

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