Endogenous retroviral insertions drive non-canonical imprinting in extra-embryonic tissues
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 lineage...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-10-01
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| Series: | Genome Biology |
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| Online Access: | http://link.springer.com/article/10.1186/s13059-019-1833-x |
| _version_ | 1818151815065108480 |
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| author | Courtney W. Hanna Raquel Pérez-Palacios Lenka Gahurova Michael Schubert Felix Krueger Laura Biggins Simon Andrews Maria Colomé-Tatché Deborah Bourc’his Wendy Dean Gavin Kelsey |
| author_facet | Courtney W. Hanna Raquel Pérez-Palacios Lenka Gahurova Michael Schubert Felix Krueger Laura Biggins Simon Andrews Maria Colomé-Tatché Deborah Bourc’his Wendy Dean Gavin Kelsey |
| author_sort | Courtney W. Hanna |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-11T13:44:49Z |
| format | Article |
| id | doaj.art-1f13e69e51574ec4ae0c64c683c949cc |
| institution | Directory Open Access Journal |
| issn | 1474-760X |
| language | English |
| last_indexed | 2024-12-11T13:44:49Z |
| publishDate | 2019-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Genome Biology |
| spelling | doaj.art-1f13e69e51574ec4ae0c64c683c949cc2022-12-22T01:04:34ZengBMCGenome Biology1474-760X2019-10-0120111710.1186/s13059-019-1833-xEndogenous retroviral insertions drive non-canonical imprinting in extra-embryonic tissuesCourtney W. Hanna0Raquel Pérez-Palacios1Lenka Gahurova2Michael Schubert3Felix Krueger4Laura Biggins5Simon Andrews6Maria Colomé-Tatché7Deborah Bourc’his8Wendy Dean9Gavin Kelsey10Epigenetics Programme, Babraham InstituteInstitut Curie, PSL University, Inserm, CNRSUniversity of South BohemiaEuropean Research Institute for the Biology of Ageing, University Medical Center Groningen, University of GroningenBioinformatics, Babraham InstituteBioinformatics, Babraham InstituteBioinformatics, Babraham InstituteEuropean Research Institute for the Biology of Ageing, University Medical Center Groningen, University of GroningenInstitut Curie, PSL University, Inserm, CNRSEpigenetics Programme, Babraham InstituteEpigenetics Programme, Babraham InstituteAbstract 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.http://link.springer.com/article/10.1186/s13059-019-1833-xGenomic imprintingHistone modificationsExtra-embryonicDevelopmentEmbryoH3K27me3 |
| spellingShingle | Courtney W. Hanna Raquel Pérez-Palacios Lenka Gahurova Michael Schubert Felix Krueger Laura Biggins Simon Andrews Maria Colomé-Tatché Deborah Bourc’his Wendy Dean Gavin Kelsey Endogenous retroviral insertions drive non-canonical imprinting in extra-embryonic tissues Genome Biology Genomic imprinting Histone modifications Extra-embryonic Development Embryo H3K27me3 |
| title | Endogenous retroviral insertions drive non-canonical imprinting in extra-embryonic tissues |
| title_full | Endogenous retroviral insertions drive non-canonical imprinting in extra-embryonic tissues |
| title_fullStr | Endogenous retroviral insertions drive non-canonical imprinting in extra-embryonic tissues |
| title_full_unstemmed | Endogenous retroviral insertions drive non-canonical imprinting in extra-embryonic tissues |
| title_short | Endogenous retroviral insertions drive non-canonical imprinting in extra-embryonic tissues |
| title_sort | endogenous retroviral insertions drive non canonical imprinting in extra embryonic tissues |
| topic | Genomic imprinting Histone modifications Extra-embryonic Development Embryo H3K27me3 |
| url | http://link.springer.com/article/10.1186/s13059-019-1833-x |
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