Gene Inactivation in Transgenic Plants—A Unique Model for Studying Epigenetic Regulation of Gene Expression

The phenomenon of transgene silencing was first observed shortly after the generation of the initial transgenic plants. The vast body of experimental data accumulated since then constitutes an invaluable resource for dissecting the mechanisms of epigenetic gene regulation. Silencing operates at either the transcriptional (TGS) or post-transcriptional (PTGS) level and is predominantly mediated by small interfering RNAs (siRNAs). Although these two epigenetic pathways involve distinct sets of proteins and enzymes, they share fundamental mechanistic features: the generation of double-stranded RNA (dsRNA), its processing into siRNAs by DICER-LIKE (DCL) enzymes, and the assembly of an Argonaute-centered effector ribonucleoprotein complex (RISC). Guided by sequence-specific siRNAs, this complex identifies complementary target sequences with high precision. A comprehensive understanding of these regulatory pathways enables the targeted induction or suppression of specific plant genes. This review traces the history of experimental findings regarding the loss of recombinant gene activity in transformants and their progeny, which collectively established the foundation for elucidating the molecular mechanisms of transgene silencing.