Review Article | Published:

Coaching from the sidelines: the nuclear periphery in genome regulation

Abstract

The genome is packaged and organized nonrandomly within the 3D space of the nucleus to promote efficient gene expression and to faithfully maintain silencing of heterochromatin. The genome is enclosed within the nucleus by the nuclear envelope membrane, which contains a set of proteins that actively participate in chromatin organization and gene regulation. Technological advances are providing views of genome organization at unprecedented resolution and are beginning to reveal the ways that cells co-opt the structures of the nuclear periphery for nuclear organization and gene regulation. These genome regulatory roles of proteins of the nuclear periphery have important influences on development, disease and ageing.

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Acknowledgements

The authors thank members of the Hetzer laboratory for providing insightful critiques on this article and apologize to those whose work could not be cited owing to space restrictions. This work was supported by US National Institutes of Health grant R01NS096786, the Nomis Foundation and the Glenn Center for Aging Research.

Reviewer information

Nature Reviews Genetics thanks J. H. Brickner, R. Wozniak and the other, anonymous reviewer(s) for their contribution to the peer review of this work.

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A.B. and J.M.K. researched data for the article. All authors contributed equally to all other aspects of this manuscript.

Correspondence to Martin W. Hetzer.

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Glossary

HiC

A technique used to study genome organization by identifying chromosomal interactions both in cis and in trans throughout the entire genome.

Nuclear periphery

The outermost region of the nucleus, which includes the nuclear envelope and associated proteins, the nuclear lamina and the nuclear pore complexes.

X chromosome inactivation

Transcriptional silencing of one X chromosome at random in XX female cells for dosage compensation between XX females and XY males.

Telomeres

Repetitive sequences found at the ends of chromosomes for maintenance of genomic integrity.

Chromatin immunoprecipitation followed by sequencing

(ChIP–seq). An assay that combines chromatin immunoprecipitation with DNA sequencing to identify protein–DNA interactions within the genome.

DNA adenine methyltransferase identification

(DamID). An assay that fuses Escherichia coli DNA adenine methyltransferase with a protein of interest to induce adenine methylation in proximity to the fusion protein. Adenine-methylated DNA fragments represent protein-binding sites within the genome.

Fluorescence in situ hybridization

(FISH). A fluorescence microscopy technique used to visualize specific genomic regions within the nucleus using fluorescently tagged DNA probes designed to hybridize to the region of interest.

Transcriptional memory

The state in which genes are poised for rapid transcriptional reactivation after an initial stimulus.

Satellite DNA

Highly repetitive non-coding sequences within heterochromatic regions of the genome.

Nucleolus

A region within the nucleus where ribosomal RNA transcription, processing and assembly occur.

Senescence

The cellular state in which cells permanently exit the cell cycle but do not undergo cell death.

Autophagy

A process in which cellular material is recycled following degradation by the lysosome or vacuole.

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Further reading

Fig. 1: Chromatin organization within the nucleus.
Fig. 2: NPC structure and dynamics.
Fig. 3: NPC-mediated gene regulation.
Fig. 4: Nuclear lamina-mediated genome organization.
Fig. 5: Nuclear decline over cellular ageing.