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The nuclear envelope and transcriptional control

Key Points

  • Chromatin mobility in eukaryotic nuclei allows rapid localization of genes in response to physiological stimuli.

  • Heritably repressed chromatin is found to be stably associated with non-pore elements of the nuclear envelope in organisms ranging from yeast to humans.

  • A subset of stress-induced genes in yeast have been shown to associate with nuclear pores during and after induction.

  • Pore-association mechanisms vary among genes, but involve both promoter elements and mRNA-surveillance and -export factors.

  • Nuclear-pore association can entail a two- to threefold increase in expression efficiency for some genes, and a more rapid reinduction after shut-off for others.

  • In male flies, gene expression on the X chromosome is enhanced twofold by the male-specific lethal (MSL) complex. This complex is associated with MTOR (Megator), a pore-associated factor.

  • MTOR and the yeast homologue MLP1 (myosin-like protein 1) are involved in mRNA elongation, which might therefore be regulated by nuclear pores.

Abstract

Cells have evolved sophisticated multi-protein complexes that can regulate gene activity at various steps of the transcription process. Recent advances highlight the role of nuclear positioning in the control of gene expression and have put nuclear envelope components at centre stage. On the inner face of the nuclear envelope, active genes localize to nuclear-pore structures whereas silent chromatin localizes to non-pore sites. Nuclear-pore components seem to not only recruit the RNA-processing and RNA-export machinery, but contribute a level of regulation that might enhance gene expression in a heritable manner.

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Figure 1: Heterochromatin in mammalian and yeast cells is distinct from nuclear pores.
Figure 2: The nuclear periphery in metazoans and yeast.
Figure 3: Telomere position through Sir4–Esc1 is independent of nuclear-pore positioning.
Figure 4: A model for the role of the NPC in coupling transcription and mRNA processing by gene looping in yeast.
Figure 5: The dosage-compensated male X chromosome in Drosophila melanogaster.

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Acknowledgements

We thank members of our laboratories for support. We are very grateful to Jop Kind for Figure 5. We apologize to any colleagues whose work could not be cited owing to space limitations. This work was support by EU funding to A.A. and S.M.G. S.M.G. acknowledges support from the Novartis Research Foundation.

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Correspondence to Asifa Akhtar or Susan M. Gasser.

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Glossary

Nuclear periphery

A term that generally refers to the nuclear-membrane bilayer, its associated proteins and the embedded nuclear-pore complexes.

Dosage compensation

A phenomenon that ensures equalized gene expression of X-chromosomal genes between males and females. In Drosophila melanogaster, this results in approximately twofold higher levels of transcriptional activation in the single male X chromosome compared with the female X chromosomes.

Nuclear lamina

A meshwork of a nuclear intermediate filament protein that is found at the interface between the inner nuclear membrane and chromatin.

Fluorescence in situ hybridization

A technique whereby a fluorescently labelled DNA probe is used to detect a particular chromosomal region by fluorescence microscopy.

Chromatin immunoprecipitation

A technique that involves crosslinking methods and is used to identify pieces of DNA or chromatin that contact a protein of interest in vivo.

Nuclear-pore complexes

Large, multiprotein complexes (composed of about 30 proteins) that are embedded in the nuclear membrane and serve as gateways for traffic between the nucleus and the cytoplasm.

MSL complex

An RNA–protein complex containing at least five male-specific Lethal (MSL) proteins, MSL1, MSL2, MSL3, MOF and MLE, and two non-coding RNAs, roX1 and roX2. This complex is stably expressed in male flies and regulates dosage compensation of X-linked genes.

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Akhtar, A., Gasser, S. The nuclear envelope and transcriptional control. Nat Rev Genet 8, 507–517 (2007). https://doi.org/10.1038/nrg2122

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