Presence of H3K4me3 on Paternally Expressed Genes of the Paternal Genome From Sperm to Implantation.

Teruhito Ishihara,Shunsuke Suzuki,Oliver W Griffith,Marilyn B Renfree

doi:10.3389/fcell.2022.838684

Abstract

Genomic imprinting, parent-of-origin-specific gene expression, is controlled by differential epigenetic status of the parental chromosomes. While DNA methylation and suppressive histone modifications established during gametogenesis suppress imprinted genes on the inactive allele, how and when the expressed allele gains its active status is not clear. In this study, we asked whether the active histone-3 lysine-4 trimethylation (H3K4me3) marks remain at paternally expressed genes (PEGs) in sperm and embryos before and after fertilization using published data. Here we show that mouse sperm had the active H3K4me3 at more than half of known PEGs, and these genes were present even after fertilization. Using reciprocal cross data, we identified 13 new transient PEGs during zygotic genome activation. Next, we confirmed that the 12 out of the 13 new transient PEGs were associated with the paternal H3K4me3 in sperm. Nine out of the 12 genes were associated with the paternal H3K4me3 in zygotes. Our results show that paternal H3K4me3 marks escape inactivation during the histone-to-protamine transition that occurs during sperm maturation and are present in embryos from early zygotic stages up to implantation.

Highlights

Genomic imprinting is regulated by differential epigenetic states between the parental alleles pretranscriptionally and controls development and maternal behavior in both eutherian and marsupial mammals (Renfree et al, 2009)
We asked if changes in histone information at paternally expressed genes (PEGs) occurred during the histone-to-protamine transition
Since some of the PEGs only retained the active H3K4me3, retaining this modification in the sperm is a common feature of these PEGs, regardless of their known maternal imprinting status in mice

Summary

Introduction

Genomic imprinting is regulated by differential epigenetic states between the parental alleles pretranscriptionally and controls development and maternal behavior in both eutherian and marsupial (therian) mammals (Renfree et al, 2009). This process evolved in the common ancestor of therian mammals and has not been found in other vertebrates. There are two major epigenetic mechanisms of genomic imprinting: differential DNA methylation and differential histone modifications. Differential DNA methylation was the first mechanism proposed for controlling genomic imprinting (Li et al, 1993). Many DNA methylation-independent imprinted genes present in eutherian mammals (Inoue et al, 2017a; Nagano et al, 2008; Wagschal et al, 2008). Characterization of the mechanisms of differential histone modification-based imprinting could shed light on the understanding of the evolution of genomic imprinting

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Conclusion