Genomic imprinting in mouse blastocysts is predominantly associated with H3K27me3

Laura Santini, Florian Halbritter, Fabian Titz-Teixeira, Toru Suzuki, Maki Asami, Xiaoyan Ma, Julia Ramesmayer, Andreas Lackner, Nick Warr, Florian Pauler, Simon Hippenmeyer, Ernest Laue, Matthias Farlik, Christoph Bock, Andreas Beyer, Anthony C. F. Perry () and Martin Leeb ()
Additional contact information
Laura Santini: Max Perutz Laboratories Vienna, University of Vienna, Vienna Biocenter
Florian Halbritter: St. Anna Children’s Cancer Research Institute (CCRI)
Fabian Titz-Teixeira: Cologne Excellence Cluster Cellular Stress Response in Aging-Associated Diseases (CECAD), University of Cologne
Toru Suzuki: University of Bath
Maki Asami: University of Bath
Xiaoyan Ma: University of Cambridge
Julia Ramesmayer: Max Perutz Laboratories Vienna, University of Vienna, Vienna Biocenter
Andreas Lackner: Max Perutz Laboratories Vienna, University of Vienna, Vienna Biocenter
Nick Warr: MRC Harwell Institute
Florian Pauler: Institute for Science and Technology Austria
Simon Hippenmeyer: Institute for Science and Technology Austria
Ernest Laue: University of Cambridge
Matthias Farlik: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
Christoph Bock: CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
Andreas Beyer: Cologne Excellence Cluster Cellular Stress Response in Aging-Associated Diseases (CECAD), University of Cologne
Anthony C. F. Perry: University of Bath
Martin Leeb: Max Perutz Laboratories Vienna, University of Vienna, Vienna Biocenter

Nature Communications, 2021, vol. 12, issue 1, 1-16

Abstract: Abstract In mammalian genomes, differentially methylated regions (DMRs) and histone marks including trimethylation of histone 3 lysine 27 (H3K27me3) at imprinted genes are asymmetrically inherited to control parentally-biased gene expression. However, neither parent-of-origin-specific transcription nor imprints have been comprehensively mapped at the blastocyst stage of preimplantation development. Here, we address this by integrating transcriptomic and epigenomic approaches in mouse preimplantation embryos. We find that seventy-one genes exhibit previously unreported parent-of-origin-specific expression in blastocysts (nBiX: novel blastocyst-imprinted expressed). Uniparental expression of nBiX genes disappears soon after implantation. Micro-whole-genome bisulfite sequencing (µWGBS) of individual uniparental blastocysts detects 859 DMRs. We further find that 16% of nBiX genes are associated with a DMR, whereas most are associated with parentally-biased H3K27me3, suggesting a role for Polycomb-mediated imprinting in blastocysts. nBiX genes are clustered: five clusters contained at least one published imprinted gene, and five clusters exclusively contained nBiX genes. These data suggest that early development undergoes a complex program of stage-specific imprinting involving different tiers of regulation.

Date: 2021
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DOI: 10.1038/s41467-021-23510-4

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