Key Points
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Chromosomes fold in a hierarchy of structures with increasing complexity, from nucleosomes and chromatin fibres to chromatin loops, chromosome domains, chromosome compartments and, finally, chromosome territories
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A limited set of components, including architectural proteins, chromatin regulators and non-coding RNAs (ncRNAs) regulate three-dimensional (3D) chromosome organization
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Chromosome architecture is globally stable, but able to receive regulatory cues to undergo local and global reorganization in specific portions of the genome
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3D organization can have causative roles in the regulation of gene expression, whereas in other cases it is modulated by gene expression
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3D chromatin structure transitions are typical of development and cell differentiation, and are often dysregulated in disease processes
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Chromosome architecture evolved considerably across evolutionary kingdoms, but remains robust in species of the distal branches of the evolutionary tree
Abstract
Understanding how chromatin is organized within the nucleus and how this 3D architecture influences gene regulation, cell fate decisions and evolution are major questions in cell biology. Despite spectacular progress in this field, we still know remarkably little about the mechanisms underlying chromatin structure and how it can be established, reset and maintained. In this Review, we discuss the insights into chromatin architecture that have been gained through recent technological developments in quantitative biology, genomics and cell and molecular biology approaches and explain how these new concepts have been used to address important biological questions in development and disease.
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Change history
31 October 2016
In the original version of this article, the statement that CCCTC-binding factor (CTCF) is conserved in most bilaterians was incorrectly referenced. Reference 58 has now been corrected in the online version of the article to cite Heger, P., Marin, B., Bartkuhn, M., Schierenberg, E. & Wiehe, T. The chromatin insulator CTCF and the emergence of metazoan diversity. Proc. Natl Acad. Sci. USA 109, 17507–17512 (2012). The authors apologize for this error.
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Acknowledgements
Research in the laboratory of G.C. was supported by grants from the European Horizon 2020 (H2020) MuG project under grant agreement No 676556, the Centre National de la Recherche Scientifique (CNRS), the European Network of Excellence EpiGeneSys, the Agence Nationale de la Recherche (EpiDevoMath), the Fondation pour la Recherche Médicale (DEI20151234396), the INSERM/Plan Cancer Epigenetics and cancer program (grant acronym “MM&TT”), the Laboratory of Excellence EpiGenMed, and the Fondation ARC pour la Recherche sur le Cancer. B.B. was funded by Sir Henry Wellcome Postdoctoral Fellowship WT100136MA.
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Glossary
- Xist region
-
Region on the X chromosome, which contains the long non-coding RNA Xist and is essential for X chromosome inactivation in placental mammals.
- Carbon copy chromosome conformation capture
-
(5C). Combines a proximity ligation chromosome conformation capture (3C) approach with amplification of interactions involving preselected sets of regions (typically two sets of hundreds to thousands of restriction fragments) to improve resolution.
- Locus control region
-
(LCR). Regulatory element that brings together multiple genes into an active chromatin hub and facilitates transcription in a cell-type-specific manner.
- Insulator proteins
-
Often present at, but not limited to, domain boundaries, insulator proteins are thought to block the interactions between regulatory elements such as enhancers and promoters. In mammals the main insulator protein is CCCTC-binding factor (CTCF), whereas in Drosophila melanogaster at least five different classes of insulator are known.
- Pre-initiation complex
-
(PIC). Large, multi-subunit protein complex that helps recruit RNA polymerase II (RNAPII) to transcription start sites and that is required for transcription.
- Bilaterians
-
All multicellular animals with bilateral symmetry.
- X chromosome inactivation
-
Dosage compensation mechanism in mammals in which one of a pair of X chromosomes is silenced.
- Boundary elements
-
DNA or epigenetic elements that are localized between two topological domains and that prevent or minimize inter-domain interactions.
- Dosage compensation
-
The process of equalizing expression output from genes located on the sex-specific chromosomes.
- Polyploidy
-
An increase in the number of chromosomes in a cell by whole-number multiples of the entire set.
- Aneuploidy
-
Aberrations in the number of chromosomes, usually accompanied by structural rearrangements.
- DNA adenine methyltransferase identification
-
(DamID). Technique to identify the binding sites of DNA- and chromatin-binding proteins in eukaryotes by fusing them to the bacterial methyltransferase enzyme Dam.
- Quantitative trait loci
-
(QTL). Regions in the genome that correlate with phenotypic variation.
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Bonev, B., Cavalli, G. Organization and function of the 3D genome. Nat Rev Genet 17, 661–678 (2016). https://doi.org/10.1038/nrg.2016.112
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DOI: https://doi.org/10.1038/nrg.2016.112
