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Hanna, C.W.* ; Pérez-Palacios, R.* ; Gahurova, L.* ; 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 Biol. 20:225 (2019)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Genomic Imprinting ; Histone Modifications ; Extra-embryonic ; Development ; Embryo ; H3k27me3 ; Non-canonical Imprinting ; Long Terminal Repeats (ltrs) ; Placenta ; Endogenous Retroviruses (ervs); Allelic Bivalent Chromatin; De-novo Methylation; Dna Methylation; Histone Modifications; Mammalian Development; Mouse; Placenta; Genome; Transcription; Receptor
ISSN (print) / ISBN 1474-760X
e-ISSN 1465-6906
Zeitschrift Genome Biology
Quellenangaben Band: 20, Heft: 1, Seiten: , Artikelnummer: 225 Supplement: ,
Verlag BioMed Central
Verlagsort Campus, 4 Crinan St, London N1 9xw, England
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Computational Biology (ICB)