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

0518783 - ÚŽFG 2020 RIV GB eng J - Článek v odborném periodiku
Hanna, C. W. - Peréz-Palacios, R. - Gahurová, Lenka - Schubert, M. - Krueger, F. - Biggins, L. - Andrews, S. - Colomé-Tatché, M. - Bourc´his, D. - Dean, W. - Kelsey, G.
Endogenous retroviral insertions drive non-canonical imprinting in extra-embryonic tissues.
Genome Biology. Roč. 20, č. 1 (2019), č. článku 225. ISSN 1474-760X. E-ISSN 1474-760X
Institucionální podpora: RVO:67985904
Klíčová slova: genomic imprinting * histone modifications * extra-embryonic
Obor OECD: Biochemistry and molecular biology
Impakt faktor: 10.806, rok: 2019
Způsob publikování: Open access
https://genomebiology.biomedcentral.com/articles/10.1186/s13059-019-1833-x

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.
Trvalý link: http://hdl.handle.net/11104/0303841