Chromosomes are not randomly folded in a spaguetti-like state in the mammalian cell nucleus, as initially thought, but occupy distinct territories. Recent studies show that these chromosome territories have preferential arrangements in different cell types, which correlate with the kinds of chromosome rearrangements that occur preferentially in each cell type. Evidence for a growing number of long-range interactions between DNA segments in the same or different chromosomes has raised the possibility of a three-dimensional network of genome interactions. As the long-range interactions described so far correlate with gene activity states, they are likely to influence and be influenced by the transcriptome of each cell type. We propose that this interchromosomal network of interactions contains epigenetic information and determines cell-type specific chromosome conformations and re-arrangements.