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- Title
Unreprogrammed H3K9me3 prevents minor zygotic genome activation and lineage commitment in SCNT embryos.
- Authors
Xu, Ruimin; Zhu, Qianshu; Zhao, Yuyan; Chen, Mo; Yang, Lingyue; Shen, Shijun; Yang, Guang; Shi, Zhifei; Zhang, Xiaolei; Shi, Qi; Kou, Xiaochen; Zhao, Yanhong; Wang, Hong; Jiang, Cizhong; Li, Chong; Gao, Shaorong; Liu, Xiaoyu
- Abstract
Somatic cell nuclear transfer (SCNT) can be used to reprogram differentiated somatic cells to a totipotent state but has poor efficiency in supporting full-term development. H3K9me3 is considered to be an epigenetic barrier to zygotic genomic activation in 2-cell SCNT embryos. However, the mechanism underlying the failure of H3K9me3 reprogramming during SCNT embryo development remains elusive. Here, we perform genome-wide profiling of H3K9me3 in cumulus cell-derived SCNT embryos. We find redundant H3K9me3 marks are closely related to defective minor zygotic genome activation. Moreover, SCNT blastocysts show severely indistinct lineage-specific H3K9me3 deposition. We identify MAX and MCRS1 as potential H3K9me3-related transcription factors and are essential for early embryogenesis. Overexpression of Max and Mcrs1 significantly benefits SCNT embryo development. Notably, MCRS1 partially rescues lineage-specific H3K9me3 allocation, and further improves the efficiency of full-term development. Importantly, our data confirm the conservation of deficient H3K9me3 differentiation in Sertoli cell-derived SCNT embryos, which may be regulated by alternative mechanisms. H3K9me3 is an epigenetic barrier to the reprogramming of somatic cells to a totipotent state during somatic cell nuclear transfer. Here, the authors uncover molecular mechanisms regulating H3K9me3 modifications in this process.
- Subjects
SOMATIC cell nuclear transfer; SOMATIC cells
- Publication
Nature Communications, 2023, Vol 14, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-023-40496-3