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RESEARCH ARTICLE |
1 Human Cytogenetics Laboratory, Imperial Cancer Research Fund, London, WC2A 3PX, UK
2 Biomolecular Modelling Laboratory, Imperial Cancer Research Fund, London, WC2A 3PX, UK
3 Mathematics and Statistics Group, Imperial Cancer Research Fund, London, WC2A 3PX, UK
4 Molecular Structure Laboratory, Imperial Cancer Research Fund, London, WC2A 3PX, UK
5 Centre for Structural Biology, Imperial College of Science, Technology and Medicine, South Kensington, London, SW7 2AZ, UK
*Authors for correspondence (e-mail: p.freemont{at}ic.ac.uk; sheer{at}icrf.icnet.uk)
Accepted July 6, 2001
Promyelocytic leukemia (PML) bodies are nuclear multi-protein domains. The observations that viruses transcribe their genomes adjacent to PML bodies and that nascent RNA accumulates at their periphery suggest that PML bodies function in transcription. We have used immuno-FISH in primary human fibroblasts to determine the 3D spatial organisation of gene-rich and gene-poor chromosomal regions relative to PML bodies. We find a highly non-random association of the gene-rich major histocompatibilty complex (MHC) on chromosome 6 with PML bodies. This association is specific for the centromeric end of the MHC and extends over a genomic region of at least 1.6 megabases. We also show that PML association is maintained when a subsection of this region is integrated into another chromosomal location. This is the first demonstration that PML bodies have specific chromosomal associations and supports a model for PML bodies as part of a functional nuclear compartment.
Key words: Immuno-FISH, Major histocompatibility complex, Nuclear organisation, PML nuclear body, Transcription
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