A significant fraction of most eukaryotic genomes is packaged into chromati
n that is not permissive for gene expression. This silent chromatin is typi
cally located near centromeres and telomeres and has fascinated scientists
for more than 70 years, yet many questions remain unanswered. Part of the d
ifficulties in studying silent chromatin at the molecular level is the repe
titive nature of the DNA sequences in these regions. To overcome this probl
em, Drosophila stocks carrying in vitro designed transgenes inserted within
silent chromatin have been generated. Molecular analysis of these transgen
es has shed light on the nature of the chromatin structure within these reg
ions and provided insights on the mechanisms of gene silencing. This review
will focus on recent studies using telomeric transgenes. The results from
these studies suggest that nuclear organization plays a role in gene silenc
ing and that silencing is the result of a block early in the process of tra
nscription initiation.