Tissue-specific spatial organization of genomes

Luis A Parada¹ , Philip G McQueen² and Tom Misteli¹

¹National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA

²Mathematical and Statistical Laboratory, Division of Computational Biology, Center for Information Technology, National Institutes of Health, Bethesda, MD 20892, USA

author email corresponding author email

Genome Biology 2004, 5:R44doi:10.1186/gb-2004-5-7-r44


Published:	21 June 2004

Subject areas: Genome studies, Molecular biology, Cell biology

Abstract

Background

Genomes are organized in vivo in the form of chromosomes. Each chromosome occupies a distinct nuclear subvolume in the form of a chromosome territory. The spatial positioning of chromosomes within the interphase nucleus is often nonrandom. It is unclear whether the nonrandom spatial arrangement of chromosomes is conserved among tissues or whether spatial genome organization is tissue-specific.

Results

Using two-dimensional and three-dimensional fluorescence in situ hybridization we have carried out a systematic analysis of the spatial positioning of a subset of mouse chromosomes in several tissues. We show that chromosomes exhibit tissue-specific organization. Chromosomes are distributed tissue-specifically with respect to their position relative to the center of the nucleus and also relative to each other. Subsets of chromosomes form distinct types of spatial clusters in different tissues and the relative distance between chromosome pairs varies among tissues. Consistent with the notion that nonrandom spatial proximity is functionally relevant in determining the outcome of chromosome translocation events, we find a correlation between tissue-specific spatial proximity and tissue-specific translocation prevalence.

Conclusions

Our results demonstrate that the spatial organization of genomes is tissue-specific and point to a role for tissue-specific spatial genome organization in the formation of recurrent chromosome arrangements among tissues.