MYC–MAX heterodimerization is essential for the induction of major zygotic genome activation and subsequent preimplantation development

Abstract In mouse preimplantation development, zygotic genome activation (ZGA), which synthesizes new transcripts in the embryo, begins in the S phase at the one-cell stage, with major ZGA occurring especially at the late two-cell stage. Myc is a transcription factor expressed in parallel with ZGA,...

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Main Authors: Takuto Yamamoto, Haoxue Wang, Hana Sato, Shinnosuke Honda, Shuntaro Ikeda, Naojiro Minami
Format: Article
Language:English
Published: Nature Portfolio 2023-09-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-023-43127-5
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author Takuto Yamamoto
Haoxue Wang
Hana Sato
Shinnosuke Honda
Shuntaro Ikeda
Naojiro Minami
author_facet Takuto Yamamoto
Haoxue Wang
Hana Sato
Shinnosuke Honda
Shuntaro Ikeda
Naojiro Minami
author_sort Takuto Yamamoto
collection DOAJ
description Abstract In mouse preimplantation development, zygotic genome activation (ZGA), which synthesizes new transcripts in the embryo, begins in the S phase at the one-cell stage, with major ZGA occurring especially at the late two-cell stage. Myc is a transcription factor expressed in parallel with ZGA, but its direct association with major ZGA has not been clarified. In this study, we found that developmental arrest occurs at the two-cell stage when mouse embryos were treated with antisense oligonucleotides targeting Myc or MYC-specific inhibitors from the one-cell stage. To identify when MYC inhibition affects development, we applied time-limited inhibitor treatment and found that inhibition of MYC at the one-cell, four-cell, and morula stages had no effect on preimplantation development, whereas inhibitor treatment at the two-cell stage arrested development at the two-cell stage. Furthermore, transcriptome analysis revealed that when MYC function was inhibited, genes expressed in the major ZGA phase were suppressed. These results suggest that MYC is essential for the induction of major ZGA and subsequent preimplantation development. Revealing the function of MYC in preimplantation development is expected to contribute to advances in assisted reproductive technology.
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spelling doaj.art-c0a10017bd534e52afe07c2019c248cb2023-11-26T13:03:23ZengNature PortfolioScientific Reports2045-23222023-09-0113111310.1038/s41598-023-43127-5MYC–MAX heterodimerization is essential for the induction of major zygotic genome activation and subsequent preimplantation developmentTakuto Yamamoto0Haoxue Wang1Hana Sato2Shinnosuke Honda3Shuntaro Ikeda4Naojiro Minami5Laboratory of Reproductive Biology, Graduate School of Agriculture, Kyoto UniversityLaboratory of Reproductive Biology, Graduate School of Agriculture, Kyoto UniversityLaboratory of Reproductive Biology, Graduate School of Agriculture, Kyoto UniversityLaboratory of Reproductive Biology, Graduate School of Agriculture, Kyoto UniversityLaboratory of Reproductive Biology, Graduate School of Agriculture, Kyoto UniversityLaboratory of Reproductive Biology, Graduate School of Agriculture, Kyoto UniversityAbstract In mouse preimplantation development, zygotic genome activation (ZGA), which synthesizes new transcripts in the embryo, begins in the S phase at the one-cell stage, with major ZGA occurring especially at the late two-cell stage. Myc is a transcription factor expressed in parallel with ZGA, but its direct association with major ZGA has not been clarified. In this study, we found that developmental arrest occurs at the two-cell stage when mouse embryos were treated with antisense oligonucleotides targeting Myc or MYC-specific inhibitors from the one-cell stage. To identify when MYC inhibition affects development, we applied time-limited inhibitor treatment and found that inhibition of MYC at the one-cell, four-cell, and morula stages had no effect on preimplantation development, whereas inhibitor treatment at the two-cell stage arrested development at the two-cell stage. Furthermore, transcriptome analysis revealed that when MYC function was inhibited, genes expressed in the major ZGA phase were suppressed. These results suggest that MYC is essential for the induction of major ZGA and subsequent preimplantation development. Revealing the function of MYC in preimplantation development is expected to contribute to advances in assisted reproductive technology.https://doi.org/10.1038/s41598-023-43127-5
spellingShingle Takuto Yamamoto
Haoxue Wang
Hana Sato
Shinnosuke Honda
Shuntaro Ikeda
Naojiro Minami
MYC–MAX heterodimerization is essential for the induction of major zygotic genome activation and subsequent preimplantation development
Scientific Reports
title MYC–MAX heterodimerization is essential for the induction of major zygotic genome activation and subsequent preimplantation development
title_full MYC–MAX heterodimerization is essential for the induction of major zygotic genome activation and subsequent preimplantation development
title_fullStr MYC–MAX heterodimerization is essential for the induction of major zygotic genome activation and subsequent preimplantation development
title_full_unstemmed MYC–MAX heterodimerization is essential for the induction of major zygotic genome activation and subsequent preimplantation development
title_short MYC–MAX heterodimerization is essential for the induction of major zygotic genome activation and subsequent preimplantation development
title_sort myc max heterodimerization is essential for the induction of major zygotic genome activation and subsequent preimplantation development
url https://doi.org/10.1038/s41598-023-43127-5
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