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REVIEW: The 4D Nucleome: Genome Compartmentalization in an Evolutionary Context

T. Cremer1*, M. Cremer1, and C. Cremer2

1Biocenter, Department of Biology II, Ludwig Maximilian University (LMU), Munich, 82152 Martinsried, Germany; E-mail: thomas.cremer@lrz.uni-muenchen.de, marion.cremer@lrz.uni-muenchen.de

2Institute of Molecular Biology (IMB) Mainz, 55128 Mainz, Germany; E-mail: c.cremer@imb-mainz.de

* To whom correspondence should be addressed.

Received November 29, 2017
4D nucleome research aims to understand the impact of nuclear organization in space and time on nuclear functions, such as gene expression patterns, chromatin replication, and the maintenance of genome integrity. In this review we describe evidence that the origin of 4D genome compartmentalization can be traced back to the prokaryotic world. In cell nuclei of animals and plants chromosomes occupy distinct territories, built up from ~1 Mb chromatin domains, which in turn are composed of smaller chromatin subdomains and also form larger chromatin domain clusters. Microscopic evidence for this higher order chromatin landscape was strengthened by chromosome conformation capture studies, in particular Hi-C. This approach demonstrated ~1 Mb sized, topologically associating domains in mammalian cell nuclei separated by boundaries. Mutations, which destroy boundaries, can result in developmental disorders and cancer. Nucleosomes appeared first as tetramers in the Archaea kingdom and later evolved to octamers built up each from two H2A, two H2B, two H3, and two H4 proteins. Notably, nucleosomes were lost during the evolution of the Dinoflagellata phylum. Dinoflagellate chromosomes remain condensed during the entire cell cycle, but their chromosome architecture differs radically from the architecture of other eukaryotes. In summary, the conservation of fundamental features of higher order chromatin arrangements throughout the evolution of metazoan animals suggests the existence of conserved, but still unknown mechanism(s) controlling this architecture. Notwithstanding this conservation, a comparison of metazoans and protists also demonstrates species-specific structural and functional features of nuclear organization.
KEY WORDS: 4D nucleome, nuclear architecture, evolution, chromatin domains, topologically associating domains (TADs), genome compartmentalization

DOI: 10.1134/S000629791804003X