2018
DOI: 10.1038/s41467-018-05841-x
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LTR retrotransposons transcribed in oocytes drive species-specific and heritable changes in DNA methylation

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-spe… Show more

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Cited by 74 publications
(107 citation statements)
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“…4 bases were removed from the 5' end of PBAT sequences. All publicly available NGS data (Supplemental Table 2) was reprocessed as above, with the exception of WGBS datasets from sperm 2 , oocytes 31 , parthenones 43 and primordial germ cells 46 , which were previously processed and filtered using identical parameters as in this study.…”
Section: Embryos (Supplementalmentioning
confidence: 99%
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“…4 bases were removed from the 5' end of PBAT sequences. All publicly available NGS data (Supplemental Table 2) was reprocessed as above, with the exception of WGBS datasets from sperm 2 , oocytes 31 , parthenones 43 and primordial germ cells 46 , which were previously processed and filtered using identical parameters as in this study.…”
Section: Embryos (Supplementalmentioning
confidence: 99%
“…As in sperm, CGIs in oocytes are generally hypomethylated and harbor nucleosomes enriched for H3K4me3 36 and/or H3K27me3 40,41 . However, a subset of CGIs, are de novo methylated in growing oocytes by DNMT3A, which is highly expressed in oocytes [42][43][44] . Paradoxically, despite widespread DNAme loss from the paternal genome in mouse zygotes, maternal DNMT3A is also clearly detected in the paternal pronucleus at this stage 14,27 and ongoing de novo DNAme is required for maintaining paternal allele DNAme of the paternally imprinted H19 locus in early embryos 45 .…”
Section: Introductionmentioning
confidence: 99%
“…Such LTRs function as oocyte-specific promoters for both novel protein-coding genes and non-coding transcripts, the latter of which are widely distributed in intergenic regions 3,17,18 . We recently identified numerous LTR-initiated transcription units (LITs) in mouse oocytes associated with H3K36me3-coupled de novo DNAme 19 . Notably, CpG islands (CGIs) embedded within such LITs also become hypermethylated by de novo DNAme in oocytes 19 and the majority of maternal igDMRs associated with paternally expressed genes in both mice and humans overlap with CGIs 14,20 .…”
Section: Lits and The Establishment Of Species-specific Imprintsmentioning
confidence: 99%
“…We recently identified numerous LTR-initiated transcription units (LITs) in mouse oocytes associated with H3K36me3-coupled de novo DNAme 19 . Notably, CpG islands (CGIs) embedded within such LITs also become hypermethylated by de novo DNAme in oocytes 19 and the majority of maternal igDMRs associated with paternally expressed genes in both mice and humans overlap with CGIs 14,20 . Since ERVs are highly variable among mammalian species and de novo DNAme at maternal igDMRs is transcription-coupled, we hypothesized that active LTRs and their associated LITs may have played an important role in the genesis of lineage-specific maternal imprinting in mammals.…”
Section: Lits and The Establishment Of Species-specific Imprintsmentioning
confidence: 99%
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