Promoter-Targeted Small Activating RNAs Alter Nucleosome Positioning

Epigenetic modification of target promoters has been identified as a mechanism underlying RNA activation (RNAa) induced by promoter-targeting small activating RNAs (saRNAs), but it is unclear how the chromosomal environment influences gene expression. In a study of the activation of the OCT4, SOX2, and NANOG genes by saRNAs, we found that saRNA targeting induced nucleosome-depleted region (NDRs) and the accumulation of RNA polymerase II (RNAPII) near or at the saRNA target sites. Additionally, promoters containing certain cis-regulatory elements such as the TATA box and CpG islands (CGIs) appeared to be more susceptible to RNAa. These results provide novel insight into the mechanism underlying RNAa in that saRNAs induce NDRs in the target promoter to remove nucleosome barriers between RNAPII-binding sites and the transcription start site (TSS), resulting in rapid assembly of transcription preinitiation complex (PIC) and subsequent activation of transcription.