Genetic information is passed on to the offspring through the oocyte and 49sperm (gametes) and greatly contributes to their phenotypes and disease susceptibility. Recent studies have revealed that the parental genomes are ac-companied by epigenetic information that is also passed on to the next genera-tion. Defects in epigenetic inheritance lead to various phenotypes in prenatal and postnatal growth in mice. This raises the possibility that epigenetic changes in gametes, possibly induced by the parental environment, might influence dis-ease susceptibility in the offspring via epigenetic inheritance mechanisms.Our laboratory is studying the mechanisms and functions of intergenera-tional inheritance of histone post-translational modifications (hPTMs) in mammals. Our specific aims are as follows (Figure): (1) To understand the molecular basis and functions of hPTM establishment and inheritance during gametogenesis and early embryogenesis. (2) To link hPTM inheritance to the pre- and peri-conceptional parental environment; (3) To understand how the parental environment might influence disease susceptibility in the offspring. To address these questions, we integrate cutting-edge low-input epigenomic technologies, reproductive engineering techniques, and various genome/epig-enome-modified mouse models. This study will not only reveal how parental lifestyle influences epigenetic memory and gene expression in germ cells but will also call for an evaluation of the contribution of epigenetic mechanisms to hereditary diseases. It will provide a basis for new approaches to preventive and predictive medicine.Figure: Parental programming hypothesisParental epigenomes are established during gameto-genesis and partially inherited by embryos to regulate gene expression in the fetus and placenta. Our lab investigates the mechanisms and functions of histone modification inheritance and the effects of the pre-/peri-conceptional parental environment on epigenetic inheritance and disease predisposition in the offspring.Recent Major PublicationsInoue A. Noncanonical imprinting: intergenerational epigenetic inheritance mediated by Polycomb com-plexes. Curr Opin Genet Dev 78, 102015 (2023)Hayashi R, Inoue A. Low-input CUT&RUN for Mouse Oocytes and Preimplantation Embryos. Methods Mol Biol 2577, 83-92. (2022)Matoba S, Kozuka C, Miura K, Inoue K, Kumon M, Hayashi R, Ohhata T, Ogura A, Inoue A. Noncanonical im-printing sustains embryonic development and restrains placental overgrowth. Genes Dev 36, 483-494 (2022)Invited presentationsInoue A. “Mechanisms of inheritable epigenome in mouse oocytes” The 95th meeting of Japanese Society of Genetics (Kumamoto, Japan) September 2023Inoue A. “Genomic imprinting mediated by maternal Polycomb complexes” INSTITUTE OF EPIGENETICS AND STEM CELLS (IES) Helmholtz Zentrum München, Invited seminar (München, Germany) June 2023Inoue A. “Genomic imprinting mediated by maternal Polycomb complexes” Max Planck Institute Munich, Invited seminar (München, Germany) June 2023Inoue A. “Maternal Polycomb complexes regulate imprinted XCI” EMBO Workshop “X-chromosome inac-tivation: New insights on its 60th anniversary” (Berlin, Germany) June 2023Inoue A. “Genomic imprinting mediated by maternal histone modifications” The 2nd Subhash Mukhopadhyay Symposium (India/Online) January 2023Laboratory for Epigenome InheritanceTeam Leader: Azusa Inoue
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