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Status |
Public on Jul 10, 2023 |
Title |
Unreprogrammed H3K9me3 prevents minor zygotic genome activation and lineage commitment in SCNT embryos |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
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.
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Overall design |
Smart-seq in somatic cell nuclear transfer (NT) embryos and morpholino knock down Max and Mcrs1 in fertilized blastocyst embryos.
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Contributor(s) |
Xv R, Zhu Q |
Citation(s) |
37558707 |
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Submission date |
Jan 31, 2022 |
Last update date |
Oct 09, 2023 |
Contact name |
Qianshu Zhu |
E-mail(s) |
zhuqianshu@tongji.edu.cn
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Organization name |
Tongji University
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Department |
School of Life Science and Technology
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Street address |
Siping Road
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City |
Shanghai |
State/province |
Shanghai |
ZIP/Postal code |
270000 |
Country |
China |
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Platforms (1) |
GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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Samples (68)
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This SubSeries is part of SuperSeries: |
GSE195762 |
Unreprogrammed H3K9me3 prevents minor zygotic genome activation and lineage commitment in SCNT embryos |
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Relations |
BioProject |
PRJNA802118 |