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

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 Mochida and Atsuo Ogura ()
Additional contact information
Kimiko Inoue: RIKEN
Narumi Ogonuki: RIKEN
Satoshi Kamimura: RIKEN
Hiroki Inoue: RIKEN
Shogo Matoba: RIKEN
Michiko Hirose: RIKEN
Arata Honda: RIKEN
Kento Miura: RIKEN
Masashi Hada: RIKEN
Ayumi Hasegawa: RIKEN
Naomi Watanabe: RIKEN
Yukiko Dodo: RIKEN
Keiji Mochida: RIKEN
Atsuo Ogura: RIKEN

Nature Communications, 2020, vol. 11, issue 1, 1-12

Abstract: 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.

Date: 2020
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16044-8

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DOI: 10.1038/s41467-020-16044-8

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