Abstract
Precise patterns of gene expression in metazoans are controlled by three classes of regulatory elements: promoters, enhancers and boundary elements. During differentiation and development, these elements form specific interactions in dynamic higher-order chromatin structures. However, the relationship between genome structure and its function in gene regulation is not completely understood. Here we review recent progress in this field and discuss whether genome structure plays an instructive role in regulating gene expression or is a reflection of the activity of the regulatory elements of the genome.
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Change history
14 October 2021
A Correction to this paper has been published: https://doi.org/10.1038/s41576-021-00425-w
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Acknowledgements
The authors thank R. A. Beagrie, J. M. Brown and M. T. Kassouf for insightful comments on the manuscript. The authors apologize to colleagues whose important studies they were unable to cite due to space constraints. This work was supported by the Max Planck Society (A.M.O.) and the UK Medical Research Council (D.H.; MR/T014067/1).
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Glossary
- Epigenetic
-
Pertains to changes in chromatin that register, signal or perpetuate altered activity states without changing the primary DNA sequence.
- Chromatin
-
The complex of DNA and proteins that makes up chromosomes; chromatin consists of nucleosomes formed of ~150 bp of DNA wrapped around a histone octamer, which can be further packaged into higher-order structures.
- Euchromatin
-
A relatively loosely packaged form of chromatin that is enriched in genes that are actively transcribed or poised for transcription.
- Facultative heterochromatin
-
Regions of chromatin that are densely packaged and transcriptionally silent but may lose their condensed state and become transcriptionally active.
- Constitutive heterochromatin
-
Regions of permanently densely packaged and transcriptionally silent chromatin that are found at specific, highly repetitive regions of the genome, such as telomeres and centromeres.
- Pre-initiation complex
-
A large complex of proteins, including RNA polymerase II and its associated general transcription factors, which is necessary for the transcription of protein-coding genes.
- TATA box
-
Named after its conserved DNA sequence, the TATA box is a non-coding DNA sequence found in many eukaryotic core promoters that recruits the pre-initiation complex to initiate transcription.
- CpG islands
-
Regions of the genome (~300–3,000 bp) that contain a large number of CpG dinucleotides and are associated with ~40–70% of mammalian gene promoters.
- Mediator complex
-
A large protein complex that acts as a key transcriptional co-activator by communicating signals from transcription factors to RNA polymerase II to control its activity.
- Nuclear speckles
-
Non-membrane-bound subdomains located in the interchromatin regions of the nucleus of mammalian cells that are enriched in splicing factors and other mRNA-processing proteins.
- Phase separation
-
The process by which substances in a mixture become separated in two distinct phases, as occurs in a mixture of oil and water.
- Polycomb
-
The Polycomb system involves various protein complexes, including Polycomb repressive complex 1 (PRC1) and PRC2, which act as transcriptional repressors with a key role in epigenetic silencing during differentiation and development.
- Polycomb bodies
-
Foci of Polycomb group proteins in the nucleus that are involved in both genome organization and repression of gene expression.
- Molecular condensates
-
Non-membrane-bound subcompartments in the nucleoplasm or cytoplasm that are strongly enriched in or depleted of specific proteins or nucleic acids.
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Oudelaar, A.M., Higgs, D.R. The relationship between genome structure and function. Nat Rev Genet 22, 154–168 (2021). https://doi.org/10.1038/s41576-020-00303-x
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DOI: https://doi.org/10.1038/s41576-020-00303-x
