Endogenous retroviral insertions drive non-canonical imprinting in extra-embryonic tissues

Courtney W. Hanna*, Raquel Perez-Palacios, Lenka Gahurova, Michael Schubert, Felix Krueger, Laura Biggins, Simon Andrews, Maria Colome-Tatche, Deborah Bourc'his, Wendy Dean, Gavin Kelsey

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

55 Citaten (Scopus)
169 Downloads (Pure)

Samenvatting

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 postimplantation 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.

Originele taal-2English
Artikelnummer225
Aantal pagina's17
TijdschriftGenome Biology
Volume20
Nummer van het tijdschrift1
DOI's
StatusPublished - 29-okt.-2019

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