Endogenous retroviral insertions drive non-canonical imprinting in extra-embryonic tissues
| dc.contributor.author | Hanna, Courtney W | |
| dc.contributor.author | Pérez-Palacios, Raquel | |
| dc.contributor.author | Gahurova, Lenka | |
| dc.contributor.author | Schubert, Michael | |
| dc.contributor.author | Krueger, Felix | |
| dc.contributor.author | Biggins, Laura | |
| dc.contributor.author | Andrews, Simon | |
| dc.contributor.author | Colomé-Tatché, Maria | |
| dc.contributor.author | Bourc’his, Deborah | |
| dc.contributor.author | Dean, Wendy | |
| dc.contributor.author | Kelsey, Gavin | |
| dc.date.accessioned | 2019-11-03T01:13:00Z | |
| dc.date.available | 2019-11-03T01:13:00Z | |
| dc.date.issued | 2019-10-29 | |
| dc.date.updated | 2019-11-03T01:13:00Z | |
| dc.description.abstract | Abstract Background Genomic imprinting is an epigenetic phenomenon that allows a subset of genes to be expressed mono-allelically based on the parent of origin and is typically regulated by differential DNA methylation inherited from gametes. Imprinting is pervasive in murine extra-embryonic lineages, and uniquely, the imprinting of several genes has been found to be conferred non-canonically through maternally inherited repressive histone modification H3K27me3. However, the underlying regulatory mechanisms of non-canonical imprinting in post-implantation development remain unexplored. Results We identify imprinted regions in post-implantation epiblast and extra-embryonic ectoderm (ExE) by assaying allelic histone modifications (H3K4me3, H3K36me3, H3K27me3), gene expression, and DNA methylation in reciprocal C57BL/6 and CAST hybrid embryos. We distinguish loci with DNA methylation-dependent (canonical) and independent (non-canonical) imprinting by assaying hybrid embryos with ablated maternally inherited DNA methylation. We find that non-canonical imprints are localized to endogenous retrovirus-K (ERVK) long terminal repeats (LTRs), which act as imprinted promoters specifically in extra-embryonic lineages. Transcribed ERVK LTRs are CpG-rich and located in close proximity to gene promoters, and imprinting status is determined by their epigenetic patterning in the oocyte. Finally, we show that oocyte-derived H3K27me3 associated with non-canonical imprints is not maintained beyond pre-implantation development at these elements and is replaced by secondary imprinted DNA methylation on the maternal allele in post-implantation ExE, while being completely silenced by bi-allelic DNA methylation in the epiblast. Conclusions This study reveals distinct epigenetic mechanisms regulating non-canonical imprinted gene expression between embryonic and extra-embryonic development and identifies an integral role for ERVK LTR repetitive elements. | |
| dc.identifier.citation | Genome Biology. 2019 Oct 29;20(1):225 | |
| dc.identifier.doi | https://doi.org/10.1186/s13059-019-1833-x | |
| dc.identifier.uri | http://hdl.handle.net/1880/111193 | |
| dc.identifier.uri | https://doi.org/10.11575/PRISM/45296 | |
| dc.language.rfc3066 | en | |
| dc.rights.holder | The Author(s). | |
| dc.title | Endogenous retroviral insertions drive non-canonical imprinting in extra-embryonic tissues | |
| dc.type | Journal Article |
