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The ‘nuclear side’ of RNA interference (RNAi) is increasingly recognized as an integral part of RNA-mediated gene silencing networks. Current data are consistent with the idea that epigenetic changes, such as DNA (cytosine-5) methylation and histone modifications, can be targeted to identical DNA sequences by short RNAs derived via Dicer cleavage of double-stranded RNA (dsRNA). To determine the relationships among RNA signals, DNA methylation and chromatin structure, we are carrying out a genetic analysis of RNA-mediated transcriptional gene silencing (TGS) in Arabidopsis. Results obtained so far indicate that in response to RNA signals, different site-specific DNA methyltransferases (DMTases) cooperate with each other and eventually with histone-modifying enzymes to establish and maintain a transcriptionally inactive state at a homologous target promoter. Processing of dsRNA in Arabidopsis …