Perturbation of nuclear architecture by long-distance chromosome interactions.
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.
Dernburg
A F
AF
Department of Biochemistry and Biophysics, University of California, San Francisco, California 94143-0554, USA.
Broman
K W
KW
Fung
J C
JC
Marshall
W F
WF
Philips
J
J
Agard
D A
DA
Sedat
J W
JW
D000818:Animals; D001483:Base Sequence; D002467:Cell Nucleus / Q000648:ultrastructure*; D002875:Chromosomes / Q000235:genetics* / Q000648:ultrastructure*; D015342:DNA Probes / Q000235:genetics; D004330:Drosophila / Q000235:genetics* / Q000254:growth & development / Q000648:ultrastructure*; D005127:Eye Color / Q000235:genetics; D005260:Female; D018507:Gene Expression Regulation, Developmental; D017344:Genes, Insect; D006570:Heterochromatin / Q000235:genetics / Q000648:ultrastructure; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D018895:Microsatellite Repeats; D008957:Models, Genetic; D013269:Stochastic Processes
D015342:DNA Probes; D006570:Heterochromatin