By capitalizing on the initially puzzling observations of unpredictable tra
nsgene silencing and variable expression, plant scientists have pioneered r
esearch into a navel type of epigenetic regulation, termed homology-depende
nt gene silencing. This silencing process has implications for natural mech
anisms of gene expression in plants and other eukaryotes, and has branched
out into studies of reversible DNA modifications; RNA metabolism, transport
and processing; and host responses to plant viruses, viroids and transposa
ble elements. The analysis of transgene silencing systems has enriched our
understanding of other epigenetic phenomena, including paramutation, as wel
l as heterosis and genome evolution. This research is also highly relevant
to the biotechnology industry, which is interested in avoiding unwanted tra
nsgene silencing in genetically engineered lines and in exploiting various
types of silencing to inactivate specific genes, Homology-dependent gene si
lencing can also be used in high-throughput approaches for functional genom
ics.