PML bodies associate specifically with the MHC gene cluster in interphase nuclei

Promyelocytic leukemia (PML) bodies are nuclear multiprotein domains. The o bservations that viruses transcribe their genomes; adjacent to PML bodies a nd that nascent RNA accumulates at their periphery suggest that PML bodies function in transcription. We have used immunoFISH in primary human fibrobl asts to determine the 3D spatial organisation of gene-rich and gene-poor ch romosomal regions relative to PML bodies. We find a highly non-random assoc iation 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 al so show that PML association is maintained when a subsection of this region is integrated into another chromosomal location. This is the first demonst ration that PML bodies have specific chromosomal associations and supports a model for PML bodies as part of a functional nuclear compartment.