RT Journal Article SR Electronic T1 Diverse mechanisms for epigenetic imprinting in mammals JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.04.30.442087 DO 10.1101/2021.04.30.442087 A1 Andergassen, Daniel A1 Smith, Zachary D. A1 Rinn, John L. A1 Meissner, Alexander YR 2021 UL http://biorxiv.org/content/early/2021/04/30/2021.04.30.442087.abstract AB Genomic imprinting and X chromosome inactivation (XCI) require epigenetic mechanisms to direct allele-specific expression. Despite their critical roles in embryonic development, how universal epigenetic regulators coordinate these specific tasks from single locus to chromosome-scale remains understudied. Here, we systematically disrupted multiple essential epigenetic pathways within polymorphic F1 zygotes to examine postimplantation effects on canonical and non-canonical genomic imprinting as well as X chromosome inactivation. We find that DNA methylation and Polycomb group repressors are both indispensable for autosomal imprinting, albeit at distinct gene sets. Moreover, the extraembryonic ectoderm relies on a broader spectrum of unique imprinting mechanisms, including non-canonical targeting of maternal endogenous retrovirus (ERV) driven promoters by G9a. We further utilize our data to identify Polycomb dependent and independent gene clusters on the imprinted X chromosome, which appears to reflect distinct domains of Xist-mediated suppression. Our data has allowed us to assemble a comprehensive inventory of the epigenetic mechanisms utilized in eutherian mammals to maintain parent-specific imprinting, including an expanded view of the placental lineage that comprises multiple unique pathways.Competing Interest StatementThe authors have declared no competing interest.