Do repeated arrays of regulatory small-RNA genes elicit genomic imprinting?: Concurrent emergence of large clusters of small non-coding RNAs and genomic imprinting at four evolutionarily distinct eutherian chromosomal loci.

The basic premise of the host-defense theory is that genomic imprinting, the parent-of-origin expression of a subset of mammalian genes, derives from mechanisms originally dedicated to silencing repeated and retroviral-like sequences that deeply colonized mammalian genomes. We propose that large clusters of tandemly-repeated C/D-box small nucleolar RNAs (snoRNAs) or microRNAs represent a novel category of sequences recognized as "genomic parasites", contributing to the emergence of genomic imprinting in a subset of chromosomal regions that contain them. Such a view is supported by evidence derived from studies of the imprinted snoRNA- and/or miRNA-encoding Dlk1-Dio3, Snurf-Snrpn, Sfbmt2, and C19MC domains. While adding a new piece to the challenging puzzle of mammalian genome history, this hypothesis also reinforces the notion that dissecting the features and molecular mechanisms that discriminate between "foreign" and "endogenous" sequences is of crucial importance in the field of mammalian epigenetics.