Territories were so named based on microscopists' early observations: that individual chromosomes did not spread out over an entire nucleus. DNA labeling also indicated that nuclei had gaps between DNA, although it was not clear if these were between DNA of the same or different chromosomes. Still, this was enough to spark talk of an interchromatin domain separating territories. “In this model, it will always be right because two pieces of chromosome will never be in exactly the same place,” says Pombo. “The field couldn't move forward.”
She and Branco responded by labeling two different chromosomes in ultrathin slices and following up with EM for even higher resolution. Based on extrapolation, an average of 46% of each chromosome territory intermingles with other chromosomes. Furthermore, extents of intermingling for different chromosomes correlated with translocation frequencies.
The nucleus is not a complete tangled mess, however. “Chromosomes as polymers will tend to expand,” says Pombo. “But what stops them is interaction with each other and with the nuclear membrane.” She is now seeing if transcription factories help keep particular chromosomes fixed to themselves or each other.