Identical cells with different 3D genomes; cause and consequences?

The mammalian genome is folded into topological domains, chromosomal units that probably serve to spatially accommodate enhancer-promoter interactions and control gene expression levels across cell populations. Longer-range contacts beyond topological domains are also formed, but only in subpopulations of cells. We propose a model (dog-on-a-lead model) to understand the principles behind and consequences of cell-specific remote DNA contacts and speculate that cell-specific genome topologies can cause variegated gene expression among otherwise identical cells.