Figure 2.

Role for LTRs in genomic imprinting. Endogenous retroviral LTRs have been demonstrated to be essential in both the setting of imprinted differentially methylated regions (DMRs) in the germline (A,B) and in driving imprinting gene expression at a number of loci (C,D). (A) In spermatogenesis, expression of LTR-derived small RNAs upstream of Rasgrf1 is targeted by the piRNA-PIWI silencing pathway, which in turn recruits de novo methyltransferase DNMT3B to methylate the locus. (B) In oogenesis, the widespread occurrence of LTR-derived transcripts traversing canonical promoters results in their methylation via the recruitment of DNMT3A to sites of elongating transcription. (C) Within the intron of imprinted gene H13, an LTR-derived gene (Mcts2) harbors a maternal gDMR, resulting in imprinted expression of Mcts2 from the paternal allele. The allelic transcriptional activity of Mcts2 disrupts the transcriptional elongation of H13, causing its premature polyadenylation. (D) The allelic expression of several noncanonically imprinted genes is a consequence of LTRs acting as alternative promoters, forming chimeric transcripts with nearby genes.