TY - JOUR
T1 - LTR retrotransposons transcribed in oocytes drive species-specific and heritable changes in DNA methylation
AU - Brind’Amour, Julie
AU - Kobayashi, Hisato
AU - Richard Albert, Julien
AU - Shirane, Kenjiro
AU - Sakashita, Akihiko
AU - Kamio, Asuka
AU - Bogutz, Aaron
AU - Koike, Tasuku
AU - Karimi, Mohammad M.
AU - Lefebvre, Louis
AU - Kono, Tomohiro
AU - Lorincz, Matthew C.
N1 - Funding Information:
We would like to thank Martin Hirst, Michelle Moksa (University of British Columbia), Soichiro Kumamoto (Tokyo University of Agriculture), Donald Au Yeung, and Dr. Fumihito Miura (Kyushu University, Japan) for technical assistance; Dixie Mager and Guillaume Bourque for helpful discussions; and Artem Babaian for help with the LIONS pipeline. J.B. was supported by a postdoctoral fellowship from the MSFHR. M.L. is supported by CIHR Grant MOP-133417 and Genome BC grant SOF154. L.L. is supported by CIHR Grant MOP-119357 and NSERC Discovery Grant 386979-12. H.K. is supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology (MEXT) of Japan (15H05579), including the MEXT-Supported Program for the Strategic Research Foundation at Private Universities (S0801025). T.K. and Professor Yasuhisa Matsui (Tohoku University, Japan) are jointly supported by the Japan Agency for Medical Research and Development (AMED-CREST, JP17gm0510017h).
Publisher Copyright:
© 2018, The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-018-05841-x
DO - 10.1038/s41467-018-05841-x
M3 - Article
C2 - 30127397
AN - SCOPUS:85051937773
SN - 2041-1723
VL - 9
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 3331
ER -