Novel imprints in mouse blastocysts are predominantly DNA methylation independent

Santini, L.; Halbritter, F.; Titz-Teixeira, F.; Suzuki, T.; Asami, M.; Ramesmayer, J.; Ma, X.; Lackner, A.; Warr, N.; Pauler, F.; Hippenmeyer, S.; Laue, E.; Farlik, M.; Bock, C.; Beyer, A.; Perry, A. C. F.; Leeb, M.

doi:10.1101/2020.11.03.366948

bioRxiv · 10.1101/2020.11.03.366948

Novel imprints in mouse blastocysts are predominantly DNA methylation independent

Santini, L.·Halbritter, F.·Titz-Teixeira, F.·Suzuki, T.·Asami, M.·Ramesmayer, J.·Ma, X.·Lackner, A.·Warr, N.·Pauler, F.·Hippenmeyer, S.·Laue, E.·Farlik, M.·Bock, C.·Beyer, A.·Perry, A. C. F.·Leeb, M.

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Abstract

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 (WGBS) 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.

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Santini, L., Halbritter, F., Titz-Teixeira, F., Suzuki, T., Asami, M., Ramesmayer, J., Ma, X., Lackner, A., Warr, N., Pauler, F., Hippenmeyer, S., Laue, E., Farlik, M., Bock, C., Beyer, A., Perry, A. C. F., Leeb, M.. 2020-11-05. Novel imprints in mouse blastocysts are predominantly DNA methylation independent. https://doi.org/10.1101/2020.11.03.366948

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