LTR retrotransposons transcribed in oocytes drive species-specific and heritable changes in DNA methylation

Julie Brind’Amour, Hisato Kobayashi (), Julien Richard Albert, Kenjiro Shirane, Akihiko Sakashita, Asuka Kamio, Aaron Bogutz, Tasuku Koike, Mohammad M. Karimi, Louis Lefebvre, Tomohiro Kono and Matthew C. Lorincz ()
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Julie Brind’Amour: University of British Columbia
Hisato Kobayashi: Tokyo University of Agriculture
Julien Richard Albert: University of British Columbia
Kenjiro Shirane: University of British Columbia
Akihiko Sakashita: Tokyo University of Agriculture
Asuka Kamio: Tokyo University of Agriculture
Aaron Bogutz: University of British Columbia
Tasuku Koike: Tokyo University of Agriculture
Mohammad M. Karimi: University of British Columbia
Louis Lefebvre: University of British Columbia
Tomohiro Kono: Tokyo University of Agriculture
Matthew C. Lorincz: University of British Columbia

Nature Communications, 2018, vol. 9, issue 1, 1-14

Abstract: Abstract De novo DNA methylation (DNAme) during mouse oogenesis occurs within transcribed regions enriched for H3K36me3. As many oocyte transcripts originate in long terminal repeats (LTRs), which are heterogeneous even between closely related mammals, we examined whether species-specific LTR-initiated transcription units (LITs) shape the oocyte methylome. Here we identify thousands of syntenic regions in mouse, rat, and human that show divergent DNAme associated with private LITs, many of which initiate in lineage-specific LTR retrotransposons. Furthermore, CpG island (CGI) promoters methylated in mouse and/or rat, but not human oocytes, are embedded within rodent-specific LITs and vice versa. Notably, at a subset of such CGI promoters, DNAme persists on the maternal genome in fertilized and parthenogenetic mouse blastocysts or in human placenta, indicative of species-specific epigenetic inheritance. Polymorphic LITs are also responsible for disparate DNAme at promoter CGIs in distantly related mouse strains, revealing that LITs also promote intra-species divergence in CGI DNAme.

Date: 2018
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DOI: 10.1038/s41467-018-05841-x

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