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Transgenerational inheritance of acquired epigenetic signatures at CpG islands in mice.

Author information

Affiliations

  • 1. Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA; Altos Labs, 5510 Morehouse Drive, Suite 300, San Diego, CA 92121, USA.
      Authors
    • Takahashi Y 1
    • Morales Valencia M 1
    • Takahashi K 1
    • Hatanaka F 1
    • Esteban CR 1
    • Izpisua Belmonte JC 1
    (6 authors)
  • 2. Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA; Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology and Key Laboratory of Assisted Reproduction, Ministry of Education, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China; Stem Cell Research Center, Peking University Third Hospital, Beijing 100191, China.
      Authors
    • Yu Y 2
    (1 author)
  • 3. Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA; Altos Labs, 5510 Morehouse Drive, Suite 300, San Diego, CA 92121, USA; Department of Regenerative Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuou-ku, Chiba 260-8670, Japan.
      Authors
    • Ouchi Y 3
    (1 author)
  • 4. Integrative Genomics and Bioinformatics Core, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
      Authors
    • Shokhirev MN 4
    • Lande K 4
    • Williams AE 4
    (3 authors)
  • 5. Gene Expression Laboratory, Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
      Authors
    • Fresia C 5
    • Shojima K 5
    (2 authors)
    • Show all (8)

ORCIDs linked to this article

Cell, 07 Feb 2023, 186(4):715-731.e19
https://doi.org/10.1016/j.cell.2022.12.047 PMID: 36754048 

A comment on this article appears in "Transgenerational inheritance of engineered cytosine methylation in mice." Cell Res. 2023 Jul;33(7):489-490. A comment on this article appears in "Engineering transgenerational epigenetic inheritance in mammals." Nat Rev Genet. 2023 Apr;24(4):209. A comment on this article appears in "Inheritance of epigenetic DNA marks studied in new mouse model." Nature. 2023 Mar;615(7954):800-802. Show all (4)

Abstract 

Transgenerational epigenetic inheritance in mammals remains a debated subject. Here, we demonstrate that DNA methylation of promoter-associated CpG islands (CGIs) can be transmitted from parents to their offspring in mice. We generated DNA methylation-edited mouse embryonic stem cells (ESCs), in which CGIs of two metabolism-related genes, the Ankyrin repeat domain 26 and the low-density lipoprotein receptor, were specifically methylated and silenced. DNA methylation-edited mice generated by microinjection of the methylated ESCs exhibited abnormal metabolic phenotypes. Acquired methylation of the targeted CGI and the phenotypic traits were maintained and transmitted across multiple generations. The heritable CGI methylation was subjected to reprogramming in parental PGCs and subsequently reestablished in the next generation at post-implantation stages. These observations provide a concrete step toward demonstrating transgenerational epigenetic inheritance in mammals, which may have implications in our understanding of evolutionary biology as well as the etiology, diagnosis, and prevention of non-genetically inherited human diseases.

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Read article at publisher's site: https://doi.org/10.1016/j.cell.2022.12.047

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