論文 - 詳細
| RRC ID | 86448 |
|---|---|
| 著者 | Horii T, Morita S, Hino S, Hino Y, Fukushima HS, Kobayashi R, Kimura M, Nakao M, Mizukami Y, Inoue A, Hatada I. |
| タイトル | Germline epigenome editing identifies H3K9me3 as a mediator of intergenerational DNA methylation recovery in mice. |
| ジャーナル | Nat Commun |
| Abstract |
Inter/transgenerational epigenetic inheritance is a crucial and controversial theory that could reshape the concept of genetics. To investigate this theory directly, we invent a system for targeted reprogramming of epigenetic memory in mouse sperm. Using this system, we erase DNA methylation at the differentially methylated region of the H19 gene (H19-DMR) in sperm, which causes Silver-Russell syndrome-like phenotypes in F1 offspring. Although DNA methylation is fully lost in the sperm, it is partially restored during pre-implantation development, suggesting the existence of epigenetic memory that instructs de novo DNA methylation. Importantly, targeted removal of histone modifications in zygotes reveals that tri-methylation at lysine 9 of histone H3 (H3K9me3), which is deposited shortly after fertilization, is required for the subsequent de novo DNA methylation at the H19-DMR. Thus, our study provides a robust germline editing tool, which reveals partial intergenerational inheritance and no transgenerational inheritance at the model locus. Furthermore, we identify H3K9me3 as a mediator for DNA methylation recovery also acting at imprinted loci. |
| 巻・号 | 16(1) |
| ページ | 11200 |
| 公開日 | 2025-12-25 |
| DOI | 10.1038/s41467-025-67488-9 |
| PII | 10.1038/s41467-025-67488-9 |
| PMID | 41449196 |
| PMC | PMC12741052 |
| MeSH | Animals DNA Methylation* / genetics Epigenesis, Genetic* Epigenome* / genetics Epigenome Editing Female Gene Editing* / methods Genomic Imprinting Germ Cells / metabolism Histones* / genetics Histones* / metabolism Male Mice Mice, Inbred C57BL RNA, Long Noncoding / genetics RNA, Long Noncoding / metabolism Spermatozoa / metabolism Zygote / metabolism |
| IF | 12.121 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 76 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 27.0 |
| リソース情報 | |
| 実験動物マウス | RBRC00213 |