Abstract
In eukaryotic cells, most of the genetic material is contained within a highly specialized organelle—the nucleus. A large body of evidence indicates that, within the nucleus, chromatinized DNA is spatially organized at multiple length scales. The higher-order organization of chromatin is crucial for proper execution of multiple genome functions, including DNA replication and transcription. Here, we review our current knowledge on the spatial organization of chromatin in the nucleus of mammalian cells, focusing in particular on how chromatin is radially arranged with respect to the nuclear lamina. We then discuss the possible mechanisms by which the radial organization of chromatin in the cell nucleus is established. Lastly, we propose a unifying model of nuclear spatial organization, and suggest novel approaches to test it.
Highlights
Edited by: Evi Soutoglou, INSERM U964 Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), France
We review our current knowledge on the spatial organization of chromatin in the nucleus of mammalian cells, focusing in particular on how chromatin is radially arranged with respect to the nuclear lamina
At the sub-chromosomal level, structural domains comprise megabase (Mb)-sized cytobands visible in metaphase chromosomes, and A/B compartments identified by Hi-C (Lieberman-Aiden et al, 2009), as well as smaller domains spanning from several kilobases up to a few Mb, including topologically associating domains (TADs) (Dixon et al, 2012) and long-range chromatin loops (Rao et al, 2014)
Summary
Most of the genetic material is contained within a highly specialized organelle—the nucleus. A large body of evidence indicates that, within the nucleus, chromatinized DNA is spatially organized at multiple length scales. The higher-order organization of chromatin is crucial for proper execution of multiple genome functions, including DNA replication and transcription. We review our current knowledge on the spatial organization of chromatin in the nucleus of mammalian cells, focusing in particular on how chromatin is radially arranged with respect to the nuclear lamina. We discuss the possible mechanisms by which the radial organization of chromatin in the cell nucleus is established. We propose a unifying model of nuclear spatial organization, and suggest novel approaches to test it
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