Trends in Genetics
ReviewRegulation and epigenetic control of transcription at the nuclear periphery
Section snippets
Localization at the nuclear periphery promotes transcriptional silencing and activation
The eukaryotic nucleus has different compartments, such as the nucleolus, nuclear envelope and nuclear pores, each with distinct structures and functions. The nuclear pore provides a gateway to the nucleus, enabling exchange of proteins and mRNA with the cytoplasm, whereas the nucleolus serves as the site for ribosomal component assembly and synthesis 1, 2. Subnuclear compartments or domains have also been implicated in regulation of transcription. Although transcription is regulated mainly
The nuclear pore complex
One of the most fascinating features of gene recruitment is that cells dynamically control the localization of particular parts of the genome. The mechanism(s) by which this is achieved are not only interesting in themselves, but also could have more general implications for our understanding of how genomes are spatially organized. The nuclear pore complex (NPC) has been identified as the site to which these genes are recruited [15]. The NPC is a large assembly of ∼30 core nucleoporin proteins
Gene recruitment as a means of optimal expression
Why are active genes recruited to the nuclear periphery? When INO1 gene recruitment was initially discovered, we showed that artificially tethering the gene to the nuclear envelope bypassed the requirement for a transcription factor in its activation [12]. Subsequent work from our laboratory has shown that tethering results in more rapid activation of INO1[35]. Likewise, LexA fusions to nucleoporins of the Nup84 subcomplex activate reporter genes, suggesting that localization at the NPC is
Concluding remarks and future directions
Recruitment of activated genes to the nuclear periphery in yeast is a new and exciting example of the relationship between subnuclear localization and transcriptional state. Although dynamic recruitment of activated genes to the nuclear periphery has not been described in other organisms, the conventional role of the periphery as a silencing environment needs revision. Examples from mice and Drosophila indicate that localization at the periphery is compatible with transcriptional activation 19,
Acknowledgements
We thank Rick Gaber and Eric Weiss, in addition to members of the Brickner laboratory, for helpful comments on the manuscript. We also thank George Santangelo for communicating unpublished results.
Glossary
- Mex
- mRNA export
- Mlp
- Myosin-like protein
- Mtor
- Megator
- Nic
- Nuclear pore interacting complex
- Nup
- nucleoporin
- Sac
- Suppressor of actin
- Thp
- Tho/Hpr1 phenotype
- TPR
- Translocated promoter region
- TREX
- transcription and export complex, a complex involved in cotranscriptional mRNA processing and transport, composed of the THO complex (Hpr1, Tho2, Mft1 and Thp2) and the Yra1–Sub2 complex
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