Round spermatid injection (ROSI) results in a lower birth rate than intracytoplasmic sperm injection, which has hampered its clinical application. Inefficient development of ROSI-embryos has been attributed to epigenetic abnormalities. However, the chromatin-based mechanism that underpins the low birth rate in ROSI remains to be determined. Here, we show that a repressive histone mark H3K27me3 persists from mouse round spermatids into zygotes in ROSI and that round spermatid-derived H3K27me3 is associated with less accessible chromatin and impaired gene expression in ROSI-embryos. These loci are initially marked by H3K27me3 but undergo histone modification remodelling in spermiogenesis, resulting in reduced H3K27me3 in normal spermatozoa. Therefore, the absence of the epigenetic remodelling, presumably mediated by histone turnover during spermiogenesis, leads to dysregulation of chromatin accessibility and transcription in ROSI-embryos. Thus, our results unveil a molecular logic, in which chromatin states in round spermatids impinge on chromatin accessibility and transcription in ROSI-embryos, highlighting the importance of epigenetic remodelling during spermiogenesis in successful reproduction.
Paternally inherited H3K27me3 affects chromatin accessibility in mouse embryos produced by round spermatid injection
Present address: Department of Animal Science and Biotechnology, School of Veterinary Medicine, Azabu University, Kanagawa, Japan.
- Award Group:
- Funder(s): Japan Society for the Promotion of Science, a Grant-in-Aid for Young Scientits
- Award Id(s): 19K16012
- Funder(s):
- Award Group:
- Funder(s): Ministry of Education, Culture, Sports, Science and Technology
- Award Id(s): JP19H05756
- Funder(s):
- Award Group:
- Funder(s): Canon Foundation
- Award Id(s): M20-0006
- Funder(s):
- Award Group:
- Funder(s): Asada Science Foundation
- Funder(s):
Currently Viewing Accepted Manuscript - Newer Version Available
Mizuki Sakamoto, Daiyu Ito, Rei Inoue, Sayaka Wakayama, Yasuyuki Kikuchi, Li Yang, Erika Hayashi, Rina Emura, Hirosuke Shiura, Takashi Kohda, Satoshi H. Namekawa, Takashi Ishiuchi, Teruhiko Wakayama, Masatoshi Ooga; Paternally inherited H3K27me3 affects chromatin accessibility in mouse embryos produced by round spermatid injection. Development 2022; dev.200696. doi: https://doi.org/10.1242/dev.200696
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