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Loss of H3K27me3 imprinting in the Sfmbt2 miRNA cluster causes enlargement of cloned mouse placentas

Author

Listed:
  • Kimiko Inoue

    (RIKEN
    University of Tsukuba)

  • Narumi Ogonuki

    (RIKEN)

  • Satoshi Kamimura

    (RIKEN
    National Institutes for Quantum and Radiological Science and Technology)

  • Hiroki Inoue

    (RIKEN
    National Institute of Genetics)

  • Shogo Matoba

    (RIKEN
    Tokyo University of Agriculture and Technology)

  • Michiko Hirose

    (RIKEN)

  • Arata Honda

    (RIKEN
    Kyoto University)

  • Kento Miura

    (RIKEN)

  • Masashi Hada

    (RIKEN)

  • Ayumi Hasegawa

    (RIKEN)

  • Naomi Watanabe

    (RIKEN
    University of Tsukuba)

  • Yukiko Dodo

    (RIKEN)

  • Keiji Mochida

    (RIKEN)

  • Atsuo Ogura

    (RIKEN
    University of Tsukuba
    RIKEN Cluster for Pioneering Research
    University of Tokyo)

Abstract

Somatic cell nuclear transfer (SCNT) in mammals is an inefficient process that is frequently associated with abnormal phenotypes, especially in placentas. Recent studies demonstrated that mouse SCNT placentas completely lack histone methylation (H3K27me3)-dependent imprinting, but how it affects placental development remains unclear. Here, we provide evidence that the loss of H3K27me3 imprinting is responsible for abnormal placental enlargement and low birth rates following SCNT, through upregulation of imprinted miRNAs. When we restore the normal paternal expression of H3K27me3-dependent imprinted genes (Sfmbt2, Gab1, and Slc38a4) in SCNT placentas by maternal knockout, the placentas remain enlarged. Intriguingly, correcting the expression of clustered miRNAs within the Sfmbt2 gene ameliorates the placental phenotype. Importantly, their target genes, which are confirmed to cause SCNT-like placental histology, recover their expression level. The birth rates increase about twofold. Thus, we identify loss of H3K27me3 imprinting as an epigenetic error that compromises embryo development following SCNT.

Suggested Citation

  • Kimiko Inoue & Narumi Ogonuki & Satoshi Kamimura & Hiroki Inoue & Shogo Matoba & Michiko Hirose & Arata Honda & Kento Miura & Masashi Hada & Ayumi Hasegawa & Naomi Watanabe & Yukiko Dodo & Keiji Mochi, 2020. "Loss of H3K27me3 imprinting in the Sfmbt2 miRNA cluster causes enlargement of cloned mouse placentas," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16044-8
    DOI: 10.1038/s41467-020-16044-8
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    Cited by:

    1. Weina Zhang & Mingzhu Wang & Zhiwei Song & Qianzheng Fu & Jiayu Chen & Weitao Zhang & Shuai Gao & Xiaoxiang Sun & Guang Yang & Qiang Zhang & Jiaqing Yang & Huanyin Tang & Haiyan Wang & Xiaochen Kou & , 2023. "Farrerol directly activates the deubiqutinase UCHL3 to promote DNA repair and reprogramming when mediated by somatic cell nuclear transfer," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

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