Sometimes to get the correct result, a researcher needs to knock a gene down. Not just a little knockdown, but like a Mike Tyson knockdown! (well, at least back in the days before the whole ear-biting thing.) Some clever scientists at The Scripps Research Institute may have found a way to do just that. By targeting the promoter region of the UbC gene with small RNAs, the authors of this NAR paper demonstrated gene silencing extending out to 30 days.
The process, called transcriptional gene silencing (TGS) works much like standard post-transcriptional gene silencing (PTGS), or RNAi, in that small RNAs are delivered in to cells to knockdown expression of a gene. The difference lies in the targets of those small RNAs.
TGS works by targeting the promoter of a gene, thereby blocking transcription and gene expression rather than targeting the mRNA transcript like RNAi. In their experiments the researchers found that treatment with a promoter specific small RNA also led to increased histone methylation, and later DNA methylation at the targeted locus, which they propose as a possible model for this silencing mechanism.
To further support this model, well known protein factors Ago1, DNMT1, DNMT3a and HDAC1 were all found to be involved in the process. Although many details of the mechanism have yet be worked out, the authors theorize that this may be part of an endogenous system used by non-coding RNAs to regulate transcription in a long-term way. To get the entire blow-by-blow account read Nucleic Acids Reserach, March 2009.