Model for bidirectional RNA mediated transcriptional regulation of gene expression in human cells.
(A) Bidirectional transcription is presumed to exert a controlled equilibrium of endogenous p21 gene expression, whereby the antisense transcript directs Ago-1 dependent low-level epigenetic regulation, H3K27me3, at the p21 sense/mRNA promoter.
(B) Upon suppression of the antisense transcript the directed H3K27me3 is diminished, allowing for enhanced p21 sense/mRNA transcriptional gene activation.
(C) When p21 sense/mRNA expression is suppressed, a release of regulatory pressure is exerted on the p21 antisense transcript allowing for p21 antisense directed Ago-1 and H3K27me3 enrichment at the p21 sense/mRNA promoter. Ago-1 has been observed to be required for the early stages of RNA directed transcriptional gene silencing [9], thus the early recruitment of Ago-1 to the p21 sense promoter may function as a re-enforcing loop to exert stable epigenetic silencing on p21 gene expression.