Imprinted genes are expressed from a single parental allele, with the other allele often silenced by DNA methylation (DNAme) established in the germline. While species-specific imprinted orthologues have been documented, the molecular mechanisms underlying the evolutionary switch from biallelic to imprinted expression are unknown. During mouse oogenesis, gametic differentially methylated regions (gDMRs) acquire DNAme in a transcription-guided manner. Here we show that oocyte transcription initiating in lineage-specific endogenous retroviruses (ERVs) is likely responsible for DNAme establishment at 4/6 mouse-specific and 17/110 human-specific imprinted gDMRs. The latter are divided into Catarrhini- or Hominoidea-specific gDMRs embedded within transcripts initiating in ERVs specific to these primate lineages. Strikingly, imprinting of the maternally methylated genes Impact and Slc38a4 was lost in the offspring of female mice harboring deletions of the relevant murine-specific ERVs upstream of these genes. Our work reveals an evolutionary mechanism whereby maternally silenced genes arise from biallelically expressed progenitors.
Conflict of interest statement
The authors declare no competing interests.
Maternal Regulation of Chromosomal Imprinting in AnimalsPB Singh et al. Chromosoma 128 (2), 69-80. PMID 30719566. - ReviewChromosomal imprinting requires an epigenetic system that "imprints" one of the two parental chromosomes such that it results in a heritable (cell-to-cell) change in beha …
Endogenous Retroviral Insertions Drive Non-Canonical Imprinting in Extra-Embryonic TissuesCW Hanna et al. Genome Biol 20 (1), 225. PMID 31665063.This study reveals distinct epigenetic mechanisms regulating non-canonical imprinted gene expression between embryonic and extra-embryonic development and identifies an i …
Imprinted Genes and Human Disease: An Evolutionary PerspectiveF Ubeda et al. Adv Exp Med Biol 626, 101-15. PMID 18372794. - ReviewImprinted genes have been associated with a wide range of diseases. Many of these diseases have symptoms that can be understood in the context of the evolutionary forces …
Ontogeny, Conservation and Functional Significance of Maternally Inherited DNA Methylation at Two Classes of Non-Imprinted GenesCE Rutledge et al. Development 141 (6), 1313-23. PMID 24523459.A functional role for DNA methylation has been well-established at imprinted loci, which inherit methylation uniparentally, most commonly from the mother via the oocyte. …
Hemimethylation of CpG Dyads Is Characteristic of Secondary DMRs Associated With Imprinted Loci and Correlates With 5-hydroxymethylcytosine at Paternally Methylated SequencesJ Nechin et al. Epigenetics Chromatin 12 (1), 64. PMID 31623686.We found high levels of hemimethylation to be a generalizable characteristic of secondary differentially methylated regions associated with imprinted genes. We propose th …
- MOP-133417/Gouvernement du Canada | Instituts de Recherche en Santé du Canada | CIHR Skin Research Training Centre (Skin Research Training Centre)
- MOP-119357/Gouvernement du Canada | Instituts de Recherche en Santé du Canada | CIHR Skin Research Training Centre (Skin Research Training Centre)
- RGPIN 05228-15/Gouvernement du Canada | Natural Sciences and Engineering Research Council of Canada (Conseil de Recherches en Sciences Naturelles et en Génie du Canada)
- RGPIN 386979-12/Gouvernement du Canada | Natural Sciences and Engineering Research Council of Canada (Conseil de Recherches en Sciences Naturelles et en Génie du Canada)