Convergent transcription induces transcriptional gene silencing in fission yeast and mammalian cells

We demonstrate that convergent transcription induces transcriptional gene silencing (TGS) in trans for both fission yeast and mammalian cells. This methodology has advantages over existing strategies to induce gene silencing. Previous studies in fission yeast have characterized TGS as a cis specific process involving RNA interference that maintains heterochromatic regions such as centromeres. In contrast for mammalian cells, gene silencing is known to occur by a post transcriptional mechanism employing exogenous siRNAs or endogenous microRNAs to inactivate mRNA. We now show that introduction of convergent transcription plasmids into either S. pombe or mammalian cells allows the production of dsRNA from inserted gene fragments resulting in TGS of endogenous genes. We predict that using convergent transcription to induce gene silencing will prove a generally useful strategy and allow a fuller molecular understanding of the biology of transcriptional gene silencing.