Abstract
Gene silencing in imprinted gene clusters is established by an epigenetic initiator that is often a long non-coding (lnc) RNA. The clustered organization of known imprinted genes indicates that the initiator extends imprinted silencing over broader chromosomal domains in extra-embryonic lineages compared to the embryo. We propose that extension of imprinted gene clusters may result from known epigenetic differences between extra-embryonic and embryonic lineages that alter the behavior of epigenetic initiators. New RNA sequencing technology will enable the full extent of imprinted silencing in embryonic and extra-embryonic lineages to be defined, but appropriate analysis and cell systems are required, which we define here based on a review of recent studies.