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Active genes dynamically colocalize to shared sites of ongoing transcription

Nature Genetics volume 36, pages 1065–1071 (2004)Cite this article

Abstract

The intranuclear position of many genes has been correlated with their activity state, suggesting that migration to functional subcompartments may influence gene expression. Indeed, nascent RNA production and RNA polymerase II seem to be localized into discrete foci or 'transcription factories'. Current estimates from cultured cells indicate that multiple genes could occupy the same factory, although this has not yet been observed. Here we show that, during transcription in vivo, distal genes colocalize to the same transcription factory at high frequencies. Active genes are dynamically organized into shared nuclear subcompartments, and movement into or out of these factories results in activation or abatement of transcription. Thus, rather than recruiting and assembling transcription complexes, active genes migrate to preassembled transcription sites.

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Figure 1: Transcription frequencies of genes on mouse chromosome 7.
Figure 2: Colocalization of transcribed genes on mouse chromosome 7.
Figure 3: Colocalization of genes is transcription-dependent.
Figure 4: Actively transcribed genes associate with RNAP II foci.
Figure 5: Actively transcribed genes colocalize to shared transcription factories.
Figure 6: Comparison of RNAP II foci in several tissue types and MEFs.
Figure 7: 3C analysis.
Figure 8: Model of dynamic associations of genes with transcription factories.

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Acknowledgements

We thank A. Corcoran and G. Kelsey for critical review of the manuscript; M. Weiss and Y. Kong for an Eraf genomic clone; and S. Andrews, C. Hennessy, E. Walters, S. Amoils and E. Astoul for their assistance. D.C. was supported by Biotechnology and Biological Sciences Research Council Studentships; A.H. is supported by a Medical Research Council Studentship; J.A.M. is supported by a Canadian Institute of Health Research Postdoctoral Fellowship; K.E.B. is supported by a Wellcome Trust Research Career Development Fellowship; and P.F. is a Senior Fellow of the Medical Research Council. This work was supported in part by the Medical Research Council and Biotechnology and Biological Sciences Research Council, UK.

Author information

Author notes

  1. David Carter

    Present address: Sir William Dunn School of Pathology, Oxford University, South Parks Road, Oxford, OX1 3RE, UK

  2. Susana Lopes

    Present address: The Wellcome Trust/Cancer Research UK Institute, Tennis Court Road, Cambridge, CB2 1QR, UK

Authors and Affiliations

  1. Laboratory of Chromatin and Gene Expression, The Babraham Institute, Babraham Research Campus, Cambridge, CB2 4AT, UK

    Cameron S Osborne, Lyubomira Chakalova, David Carter, Alice Horton, Emmanuel Debrand, Beatriz Goyenechea, Jennifer A Mitchell & Peter Fraser

  2. Chromosome Biology Group, Imperial College Faculty of Medicine, Hammersmith Hospital Campus, Du Cane Road, London, W12 ONN, UK

    Karen E Brown

  3. Laboratory of Developmental Genetics and Imprinting, The Babraham Institute, Babraham Research Campus, Cambridge, CB2 4AT, UK

    Susana Lopes & Wolf Reik

  4. Sir William Dunn School of Pathology, Oxford University, South Parks Road, Oxford, OX1 3RE, UK

    Susana Lopes

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Supplementary information

Supplementary Fig. 1

Distributions of 3D measurements of the separation distances between genes. (PDF 39 kb)

Supplementary Fig. 2

Positioning of active and inactive genes relative to the chromosome 7 territory. (PDF 84 kb)

Supplementary Fig. 3

Positions of Hbb, Eraf, Uros, Igf2 and Kcnq1ot1 gene loci in relation to gene dense regions of mouse chromosome 7. (PDF 85 kb)

Supplementary Table 1

Quantitation of Eraf and Uros transcription foci in erythroid cells and frequency of co-localization with Hbb foci. (PDF 2 kb)

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Osborne, C., Chakalova, L., Brown, K. et al. Active genes dynamically colocalize to shared sites of ongoing transcription. Nat Genet 36, 1065–1071 (2004). https://doi.org/10.1038/ng1423

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