  There is growing appreciation that gene function is connected to the dynamic
structure of the chromosome. Here we explore the interplay between
three-dimensional structure and transcriptional activity at the single cell
level. We show that inactive loci are spatially more compact than active ones,
and that within active loci the enhancer driving transcription is closest to
the promoter. On the other hand, even this shortest distance is too long to
support direct physical contact between the enhancer-promoter pair when the
locus is transcriptionally active. Artificial manipulation of genomic
separations between enhancers and the promoter produces changes in physical
distance and transcriptional activity, recapitulating the correlation seen in
wild-type embryos, but disruption of topological domain boundaries has no
effect. Our results suggest a complex interdependence between transcription and
the spatial organization of cis-regulatory elements.
