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Blank spots on the map: some current questions on nuclear organization and genome architecture

Abstract

The past decades have provided remarkable insights into how the eukaryotic cell nucleus and the genome within it are organized. The combined use of imaging, biochemistry and molecular biology approaches has revealed several basic principles of nuclear architecture and function, including the existence of chromatin domains of various sizes, the presence of a large number of non-membranous intranuclear bodies, non-random positioning of genes and chromosomes in 3D space, and a prominent role of the nuclear lamina in organizing genomes. Despite this tremendous progress in elucidating the biological properties of the cell nucleus, many questions remain. Here, we highlight some of the key open areas of investigation in the field of nuclear organization and genome architecture with a particular focus on the mechanisms and principles of higher-order genome organization, the emerging role of liquid phase separation in cellular organization, and the functional role of the nuclear lamina in physiological processes.

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Acknowledgements

Work in the Misteli lab was supported by funding from the Intramural Research Program of the National Institutes of Health (NIH), National Cancer Institute, and Center for Cancer Research and by the NIH 4D Nucleome Common Fund Project (5U54DK107980-01). PT was supported by the Polish National Science Centre Grants (2014/15/N/NZ2/00379 and 2017/24/T/NZ2/00307), KM was supported by a Department of Defense Idea Award (W81XWH-15-1-0322), CA was supported by an IWT fellowship (no. 141372) from the Belgian Research Foundation—Flanders (FWO) and a Gustave Boël—Sofina travel grant from the Koning Boudewijn Stichting, Belgium, SV was supported by an Erwin Schroedinger Fellowship from the Austrian Science Fund (J3849-B28), and MF is supported by a Postdoctoral Research Associate Training (PRAT) fellowship from the National Institute of General Medical Sciences (NIGMS, 1Fi2GM128585-01).

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Correspondence to Tom Misteli.

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Adriaens, C., Serebryannyy, L.A., Feric, M. et al. Blank spots on the map: some current questions on nuclear organization and genome architecture. Histochem Cell Biol 150, 579–592 (2018). https://doi.org/10.1007/s00418-018-1726-1

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  • DOI: https://doi.org/10.1007/s00418-018-1726-1

Keywords

  • Genome organization
  • Nuclear architecture
  • Phase separation
  • Nuclear lamina