E-Poster Presentation ESA-SRB-ANZBMS 2021

Can paternal H3K4me3 transmission in sperm affect imprinting status of paternally-expressed genes after fertilisation? (#576)

Teruhito Ishihara 1 , Oliver W Griffith 2 , Shunsuke Suzuki 3 , Marilyn B Renfree 1
  1. School of BioSciences, The University of Melbourne, Melbourne, VIC, Australia
  2. Department of Biological Sciences, Macquarie University, Sydney, NSW, Australia
  3. Department of Agricultural and Life Sciences, Shinshu University, Nagano, Japan

During the establishment of genomic imprinting, only one copy of the two parental alleles is activated, regulated by a differential epigenetic status of the mother’s or father’s chromosomes. While DNA methylation and suppressive histone modifications established during gametogenesis play a crucial role in supressing imprinted genes on the inactive allele, how and when the expressed allele gains its active status is not clear. It is possible that active chromatin status could be inherited from the active histone marks in gametes. However, transmission of paternal active histone marks would not occur if histones are replaced with protamine by the histone-to-protamine transition that occurs in spermatozoa in the final stages of maturation. In this study, we asked whether active histone marks remain in sperm throughout the histone-to-protamine transition and whether they remain active after fertilisation. We analysed published data to assess the active status of paternally-expressed genes. Mouse sperm retained the active histone mark, histone-3 lysine-4 tri-methylation (H3K4me3) at more than half of known paternally-expressed genes, regardless of their association with DNA methylation. The transmitted paternal histone status was retained during early embryogenesis, suggesting that the paternal H3K4me3 transmission defined active status of the paternally-expressed genes. Using reciprocal cross data, novel paternally-expressed genes during zygotic genome activation were identified. The majority of the identified paternally-expressed genes retained H3K4me3 in sperm. However, differential epigenetic status at some of the novel imprinted genes was reprogrammed as embryogenesis proceeds. The loss of differential epigenetic status between the alleles coincided with their loss of imprinted gene expression during pre-implantation development. The retention of H3K4me3 through the histone-to-protamine transition may be a mechanism for transmitting active chromatin status of paternally-expressed genes.