Cells are able to pack an amazing amount of genetic information into the small confines of the nucleus. This leads to the question of whether the way in which the genetic information is stored and packed has any bearing on gene expression. We have developed a method for measuring gene expression and chromosome structure simultaneously in single cells in an attempt to answer these questions. By tracing gene expression along a chromosome in a microscope, we found that large scale rearrangements of chromosome structure can profoundly impact gene expression over large regions of chromosomes, suggesting the existence of chromosome-scale gene regulatory mechanisms. We also discuss some preliminary results connecting transcription to cellular homeostasis.