Diverse epigenetic mechanisms maintain parental imprints within the embryonic and extraembryonic lineages

Genomic imprinting and X chromosome inactivation (XCI) require epigenetic mechanisms to encode allele-specific expression, but how these specific tasks are accomplished at single loci or across chromosomal scales remains incompletely understood. Here, we systematically disrupt essential epigenetic p...

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Bibliographic Details
Published in:Developmental cell 2021-11, Vol.56 (21), p.2995-3005.e4
Main Authors: Andergassen, Daniel, Smith, Zachary D, Kretzmer, Helene, Rinn, John L, Meissner, Alexander
Format: Article
Language:English
Subjects:
Animals
Cell Lineage - physiology
DNA Methylation - physiology
Ectoderm - metabolism
Epigenesis, Genetic - genetics
Female
Genomic Imprinting - genetics
Histones - metabolism
Mice
Placenta - metabolism
Pregnancy
RNA, Long Noncoding - genetics
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Summary:Genomic imprinting and X chromosome inactivation (XCI) require epigenetic mechanisms to encode allele-specific expression, but how these specific tasks are accomplished at single loci or across chromosomal scales remains incompletely understood. Here, we systematically disrupt essential epigenetic pathways within polymorphic embryos in order to examine canonical and non-canonical genomic imprinting as well as XCI. We find that DNA methylation and Polycomb group repressors are indispensable for autosomal imprinting, albeit at distinct gene sets. Moreover, the extraembryonic ectoderm relies on a broader spectrum of imprinting mechanisms, including non-canonical targeting of maternal endogenous retrovirus (ERV)-driven promoters by the H3K9 methyltransferase G9a. We further identify Polycomb-dependent and -independent gene clusters on the imprinted X chromosome, which appear to reflect distinct domains of Xist-mediated suppression. From our data, we assemble a comprehensive inventory of the epigenetic pathways that maintain parent-specific imprinting in eutherian mammals, including an expanded view of the placental lineage.
ISSN:1534-5807
1878-1551
DOI:10.1016/j.devcel.2021.10.010