| RRC ID |
86448
|
| Author |
Horii T, Morita S, Hino S, Hino Y, Fukushima HS, Kobayashi R, Kimura M, Nakao M, Mizukami Y, Inoue A, Hatada I.
|
| Title |
Germline epigenome editing identifies H3K9me3 as a mediator of intergenerational DNA methylation recovery in mice.
|
| Journal |
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.
|
| Volume |
16(1)
|
| Pages |
11200
|
| Published |
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
|
| Resource |
| Mice |
RBRC00213 |
