Fig. 4.

Model for RNA-directed TGS in human cells. (A) The promoter-associated RNA model of RNA-mediated TGS proposes that a variant species of mRNA, a promoter-associated mRNA, essentially containing an extended 5′ UTR, is recognized by the antisense strand of siRNAs or possibly endogenous antisense RNAs during RNAPII-mediated transcription of the RNA-targeted promoter. (B) The antisense strand of the siRNA might then guide a putative transcriptional silencing complex (possibly composed of DNMT3A, Ago-1, HDAC-1, and/or EZH2) to the targeted promoter where histone modifications result and the initial gene-silencing event. (C) The initial silencing event or prolonged suppression of the siRNA-targeted promoter may result in heterchromatization of the local siRNA-targeted genomic region and is not, based on these data, thought to be the result of slicing of the low-copy promoter-associated RNA but rather due to a recruitment of chromatin remodeling factors or complexes to the targeted promoter that result in the gene silencing event.