Figure 1.
Putative models for small RNA directed TGS in human cells. (A) The RNA/RNA model of transcriptional gene silencing is shown where the antisense strand of the small RNA either binds or associates with Ago-1 and possibly Ezh2, DNMT3a or HDAC-1 and then localizes to the elongating RNAPII expressed transcript that spans the targeted promoter loci. This model is supported by data showing that RNAPII activity and a low copy promoter associated RNA is involved in small RNA directed TGS in human cells.41,45 Alternatively, or more common at TATAA loci and transcriptional start sites the RNA/DNA model may be operative. (B) In the RNA/DNA model the antisense strand of the small RNA may localize with the transcriptional silencing complex containing Ago-1, Ezh2, DNMT3a and HDAC-1 to the genomic DNA. The localization of these components to the transcriptional start site might alter later RNAPII binding and activity. This model is supported by data showing transcriptional start sites are susceptible to small antigene RNA targeting.42