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  • Review Article
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Transcription factories: gene expression in unions?

Key Points

  • The fundamental process of gene transcription can be reconstituted in vitro, but an understanding of how it operates and how it is regulated in vivo is lacking. One hypothesis suggests that, rather than RNA polymerases being recruited to the promoters of active genes, it is the gene loci that must move to sites in the nucleus — termed transcription factories — where RNA polymerase II is anchored.

  • Cell biology approaches have driven the transcription factory model. Active genes can be seen in close spatial proximity to one another in the nucleus, at sites coincident with high concentrations of the active elongating form of RNA polymerase II. Molecular chromatin conformation capture (3C)-based approaches also indicate a spatial clustering of active genes in the cell nucleus.

  • An unanswered question is whether transcription factories are a cause or a consequence of gene expression.

  • The transcription factory model has implications for the evolution of gene order along and between chromosomes, and for the generation of chromosome translocations.

Abstract

Transcription is a fundamental step in gene expression, yet it remains poorly understood at a cellular level. Visualization of transcription sites and active genes has led to the suggestion that transcription occurs at discrete sites in the nucleus, termed transcription factories, where multiple active RNA polymerases are concentrated and anchored to a nuclear substructure. However, this concept is not universally accepted. This Review discusses the experimental evidence in support of the transcription factory model and the evidence that argues against such a spatially structured view of transcription. The transcription factory model has implications for the regulation of transcription initiation and elongation, for the organization of genes in the genome, for the co-regulation of genes and for genome instability.

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Figure 1: Model of transcription with RNA polymerase immobilized in transcription factories.
Figure 2: Model of heat shock gene activation in Drosophila melanogaster.
Figure 3: The association of transcribing globin genes.
Figure 4: Model of transcription factory associations for genes bound by poised RNAPII.

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Acknowledgements

H.S. and W.A.B. are supported by the UK Medical Research Council, the James S. McDonnell Foundation and the EU FP6 Epigenome NoE. Thanks to V. Buckle and J. Brown for supplying images for Fig. 3.

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Correspondence to Wendy A. Bickmore.

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Glossary

Fibrillar centre

A region of the nucleolus that exhibits pale staining in electron micrographs. Contains the RNAPI transcriptional machinery, and the dense fibrillar and granular components of the nucleolus form around it.

Dense fibrillar component

Electron-dense region of the nucleolus, surrounding fibrillar centres, into which ribosomal RNA transcripts are extruded. Active transcription of ribosomal DNA genes is thought to occur at the border between a fibrillar centre and the dense fibrillar component.

Erythroblast

A red blood cell type that has a nucleus and is the precursor of an erythrocyte (a red blood cell).

Erythroid cells

Cells in the lineage that give rise to erythrocytes (red blood cells).

Electron spectroscopic imaging

A form of electron microscopy on unstained sections, in which the contrast is dependent on energy loss from endogenous atoms in the specimen. This enables phosphorous and nitrogen atoms to be mapped, and hence protein and nucleic acid-rich areas can be distinguished.

Splicing factor-enriched nuclear speckles

Sites in the nucleus that contain a high concentration of proteins that are involved in the splicing of pre-mRNA into mRNA.

Balbiani ring

A large puff in polytene chromosomes from the larval salivary glands of the dipteran insect Chironomus tentans (midge).

Heat shock loci

Loci encoding proteins that are expressed when cells are exposed to stresses, including elevated temperature.

Locus control region

An upstream long-range element required for normal regulation of mammalian β-globin gene expression in erythroid cells.

Mitotic interchromatin granules

Structures in the cytoplasm of metaphase cells where pre-mRNA processing factors are seen.

Chromosome territories

Domain of the nucleus where most of the chromatin from a specific chromosome is concentrated.

Pre-initiation complex

Large complex of general transcription factors, comprising TFIIA, TFIIB, TFIID, TFIIE, TFIIF and TFIIH, that are required to recruit RNA polymerase II to transcription start sites.

RIDGES

Regions of the genome with a high concentration of highly expressed genes.

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Sutherland, H., Bickmore, W. Transcription factories: gene expression in unions?. Nat Rev Genet 10, 457–466 (2009). https://doi.org/10.1038/nrg2592

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