Perturbation of nuclear architecture by long-distance chromosome interactions

Cell. 1996 May 31;85(5):745-59. doi: 10.1016/s0092-8674(00)81240-4.


Position-effect variegation (PEV) describes the stochastic transcriptional silencing of a gene positioned adjacent to heterochromatin. Using FISH, we have tested whether variegated expression of the eye-color gene brown in Drosophila is influenced by its nuclear localization. In embryonic nuclei, a heterochromatic insertion at the brown locus is always spatially isolated from other heterochromatin. However, during larval development this insertion physically associates with other heterochromatic regions on the same chromosome in a stochastic manner. These observations indicate that the brown gene is silenced by specific contact with centromeric heterochromatin. Moreover, they provide direct evidence for long-range chromosome interactions and their impact on three-dimensional nuclear architecture, while providing a cohesive explanation for the phenomenon of PEV.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • Cell Nucleus / ultrastructure*
  • Chromosomes / genetics*
  • Chromosomes / ultrastructure*
  • DNA Probes / genetics
  • Drosophila / genetics*
  • Drosophila / growth & development
  • Drosophila / ultrastructure*
  • Eye Color / genetics
  • Female
  • Gene Expression Regulation, Developmental
  • Genes, Insect*
  • Heterochromatin / genetics
  • Heterochromatin / ultrastructure
  • In Situ Hybridization, Fluorescence
  • Male
  • Microsatellite Repeats
  • Models, Genetic
  • Stochastic Processes


  • DNA Probes
  • Heterochromatin