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.
Highlights
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
After exclusion of transcripts encoded by the X chromosome, 10,743 robustly expressed transcripts (≥12 reads in at least four out of eight samples) were identified that contained informative single nucleotide polymorphisms (SNPs)
We refer to the first group of 147 genes as blastocyst-skewed expressed (BsX), and the subset that further fulfilled the 70:30 criterion as blastocyst-imprinted expressed (BiX; n = 105) genes (Supplementary Fig. 1c)
Summary
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. In addition to DNA methylation-based genomic imprinting, a subset of genes with paternal expression bias in mouse preimplantation embryos is maternally enriched for H3K27me[3], with no apparent direct dependence on DNA methylation. We sought to determine parent-oforigin-specific expression in biparental embryos and parent-oforigin-specific DNA methylation in uniparental blastocysts to delineate the imprinting landscape in mouse preimplantation development. Superimposing these and published data on the allele-specific H3K27me[3] embryonic landscape reveals the state and provenance of imprinting in preimplantation blastocysts
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