Across kingdoms, RNA interference (RNAi) has been shown to control gene expression at the transcriptional- or the post-transcriptional level. Here, we describe mechanisms in which different classes of siRNAs trigger heterochromatin formation in trans. First, injection of truncated transgenes, unable to produce translatable mRNA, produce predominantly antisense siRNAs which depend on a variety of RNAi components. These include RDR3, HEN1 & PTIWI14 as well as a second set of components, which are also involved in post-transcriptional silencing: RDR2, PTIWI13, DCR1 and CID2. Our data indicates differential processing of nascent un-spliced and long, spliced transcripts. As transgene derived siRNAs trigger repressive histone marks at the remote loci, this suggests a functional interaction between post-transcriptional and co-transcriptional RNAi: next to a loss of H3K9ac and H3K4me3, increased levels of histone occupancy and H3K27me3 can be observed. This is accompanied by secondary siRNA accumulation, strictly limited to the open reading frame of the remote locus. Next to this exogenously triggered RNAi, also the endogenously controlled mutual exclusive expression of the surface antigen family depends on RDR3, HEN1, DCR1 and DCL4. Here, silent genes show surprisingly high levels of H3K4me3 and they exhibit very low levels of 23nt antisense RNAs. Surprisingly, actively transcribed antigen genes produce high levels of 23nt sense siRNA produced from the entire length of the mRNA. As silencing of RDR3 disrupts mutual exclusive expression as all surface antigens are co-expressed, this is accompanied with loss of sense siRNAs and accumulation of antisense siRNAs of the entire coding genome. As the data suggests that RDR3 and RDR2 compete for different classes of precursor RNAs, we classified siRNA clusters of the entire genome by their dependency on different RNAi components and compared these with chromatin data. This indicates that similar mechanisms to transgene induced silencing and serotype regulation contribute to transcriptome regulation by post-transcriptional and transcriptional silencing.