Novel imprints in mouse blastocysts are predominantly DNA methylation independent Santini, Laura Halbritter, Florian Titz-Teixeira, Fabian Suzuki, Toru Asami, Maki Ramesmayer, Julia Ma, Xiaoyan Lackner, Andreas Warr, Nick Pauler, Florian ; https://orcid.org/0000-0002-7462-0048 Hippenmeyer, Simon ; https://orcid.org/0000-0003-2279-1061 Laue, Ernest Farlik, Matthias Bock, Christoph Beyer, Andreas Perry, Anthony C. F. Leeb, Martin In mammals, chromatin marks at imprinted genes are asymmetrically inherited to control parentally-biased gene expression. This control is thought predominantly to involve parent-specific differentially methylated regions (DMR) in genomic DNA. However, neither parent-of-origin-specific transcription nor DMRs have been comprehensively mapped. We here address this by integrating transcriptomic and epigenomic approaches in mouse preimplantation embryos (blastocysts). Transcriptome-analysis identified 71 genes expressed with previously unknown parent-of-origin-specific expression in blastocysts (nBiX: novel blastocyst-imprinted expression). Uniparental expression of nBiX genes disappeared soon after implantation. Micro-whole-genome bisulfite sequencing (μWGBS) of individual uniparental blastocysts detected 859 DMRs. Only 18% of nBiXs were associated with a DMR, whereas 60% were associated with parentally-biased H3K27me3. This suggests a major role for Polycomb-mediated imprinting in blastocysts. Five nBiX-clusters contained at least one known imprinted gene, and five novel clusters contained exclusively nBiX-genes. These data suggest a complex program of stage-specific imprinting involving different tiers of regulation. 2020 info:eu-repo/semantics/preprint doc-type:preprint text http://purl.org/coar/resource_type/c_816b https://research-explorer.ista.ac.at/record/8813 Santini L, Halbritter F, Titz-Teixeira F, et al. Novel imprints in mouse blastocysts are predominantly DNA methylation independent. <i>bioRxiv</i>. doi:<a href="https://doi.org/10.1101/2020.11.03.366948">10.1101/2020.11.03.366948</a> eng info:eu-repo/semantics/altIdentifier/doi/10.1101/2020.11.03.366948 info:eu-repo/semantics/altIdentifier/pmid/PPR234457 info:eu-repo/semantics/openAccess