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PreprintCited by 10Cancer-related gene regulationDevelopmental Biology and Gene RegulationEpigenetics and DNA Methylation

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Chimeric PRMT6 protein produced by an endogenous retrovirus promoter regulates cell fate decision in mouse preimplantation embryos

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Honda, Shinnosuke, Hatamura, Maho, Kunimoto, Yuri, Ikeda, Shuntaro, Minami, Naojiro·2022·Biology of Reproduction
DOI 10.1101/2022.08.23.505038

Preprint — published as 10.1093/biolre/ioae002 · Paper page

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Abstract

Murine endogenous retrovirus with leucine tRNA primer, also known as MERVL, is expressed during zygotic genome activation in mammalian embryos. Here we show that protein arginine N-methyltransferase 6 ( Prmt6 ) forms a chimeric transcript with MT2B2, one of the long terminal repeat sequences of MERVL, and is translated into an elongated chimeric protein (PRMT6 MT2B2 ) whose function differs from that of the canonical PRMT6 protein (PRMT6 CAN ) in mouse preimplantation embryos. Overexpression of PRMT6 CAN in fibroblast cells increased asymmetric dimethylation of the third arginine residue of both histone H2A (H2AR3me2a) and histone H4 (H4R3me2a), while overexpression of PRMT6 MT2B2 increased only H2AR3me2a. In addition, overexpression of PRMT6 MT2B2 in one blastomere of mouse two-cell embryos promoted cell proliferation and differentiation of the blastomere into epiblast cells at the blastocyst stage, while overexpression of PRMT6 CAN repressed cell proliferation. This is the first report of the translation of a chimeric protein (PRMT6 MT2B2 ) in mouse preimplantation embryos. Our results suggest that analyzing chimeric transcripts with MERVL will provide insight into the relationship between zygotic genome activation and subsequent intra- and extra-cellular lineage determination.

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Metadata

Authors
Honda, S., Hatamura, M., Kunimoto, Y., Ikeda, S., & Minami, N.
Affiliations
Kyoto University (JP)
Corresponding author
Minami, Naojiro
ORCID
Venue
Biology of Reproduction
Publisher
openRxiv
Published
2022-08-24
Volume
110
Issue
4
Pages
698-710
ISSN
0006-3363 (ISSN-L)
DOI
10.1101/2022.08.23.505038
OpenAlex
W4390700046
Cited by
10
References
1
Citations by year
2026: 2 · 2025: 6 · 2024: 2
FWCI
1.36
Type
journal article
Language
en
Open access
Licence
cc-by-nc-nd
Locations
  • Biology of Reproduction (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Institutional Repositories DataBase (IRDB) (submittedVersion)
  • Kyoto University Research Information Repository (Kyoto University) (submittedVersion)
Funders
  • Japan Society for the Promotion of Science (19J23290, 19H03136, 22K20612)
  • Institute for Advanced Studies, Kasetsart University
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer-related gene regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
Keywords
PRMT6, fusion protein, MERVL, endogenous retroviruses, long terminal repeat, preimplantation embryo, cell fate determination, asymmetric dimethylation, histone H2A, histone H4, zygotic genome activation, blastocyst, cell proliferation, lineage determination
MeSH terms
Animals, Arginine, Blastocyst, Histones, Leucine, Mammals, Methylation, Recombinant Fusion Proteins, RNA, Transfer, Endogenous Retroviruses, Mice

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