Cis-acting determinants of paramutation

Paramutation is an epigenetic phenomenon whereby in trans communication between homologous sequences leads to meiotically heritable epigenetic changes at one of the alleles. Cis-acting determinants of paramutation are DNA sequences and associated epigenetic modifications that are required for paramutation. Here, we review how characteristics of the underlying DNA sequences determine whether paramutation can occur and how they affect the behavior displayed by the various paramutation phenomena. Paramutation is strongly associated with repeated sequences, especially tandemly repeated sequences. Cis-acting determinants consisting of repeated sequences are consistent with the involvement of RNA-directed DNA methylation (RdDM) in plants and the PIWI-interacting RNA (piRNA) pathway in animals. In the RdDM-based model, siRNAs produced by paramutagenic loci would reinforce the silenced state of paramutagenic loci in cis and initiate transcriptional silencing of paramutable loci in trans. In this review, we discuss how sequence characteristics and epigenetic modifications of cis-acting sequences can trigger the recruitment of silencing machineries.