Though the specific mechanisms by which paramutation acts vary from organism to organism, all well-documented cases point towards epigenetic modification and RNA-silencing as the underlying mechanism for paramutation.
In the case of the r1 locus in maize, DNA methylation of a region of tandem repeats near the coding region of the gene is characteristic of the paramutagenic B’ allele, and when the paramutable B-I allele becomes paramutagenic, it too takes on the same DNA methylation pattern. In order for this methylation to be successfully transferred, a number of genes coding for RNA-dependent RNA polymerases and other components of RNA-silencing pathways are required, suggesting that paramutation is mediated via endogenous RNA-silencing pathways. The transcription of short interfering RNAs from the tandem repeat regions corroborates this. In animal systems such as Drosophila, piRNAs have also been implicated in mediating paramutation. In addition to the characteristic DNA methylation state changes, changes in histone modification patterns in the methylated DNA regions, and/or the requirement of histone modifying proteins to mediate paramutation have also been noted in multiple systems. It has been suggested that these histone modifications play a role in maintaining the paramutated state. The previously mentioned tandem repeat region in the r1 locus is also typical of other loci showing paramutation or paramutation-like phenomena.
However, it has been noted that it is not possible to explain all occurrences and features of paramutation with what is known about RNAi-mediated transcriptional silencing, suggesting that other pathways and/or mechanisms are also at play.