Journal
CELL STEM CELL
Volume 28, Issue 1, Pages 150-+Publisher
CELL PRESS
DOI: 10.1016/j.stem.2020.09.006
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Funding
- National Key RAMP
- D Program of China [2016YFA0100400, 2019YFA0110000]
- National Natural Science Foundation of China [31721003, 81630035, 31820103009, 32070857, 31871446, 31972882, 31771419, 31871448, 32000418, 82022027, 31900621]
- Young Elite Scientist Sponsorship Program by CAST [2018QNRC001]
- key project of the Science and Technology of Shanghai Municipality [19JC1415300]
- Shanghai Rising-Star Program [19QA1409600, 17QA1402700]
- Shanghai municipal medical and health discipline construction projects [2017ZZ02015]
- Shanghai Zhangjiang National Innovation Demonstration Zone [ZJ2018-ZD-004]
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The reprogramming of H3K9ac is crucial for optimal SCNT efficiency. TSA corrects aberrant acetylation in SCNT embryos, while the overexpression of Dux greatly improves efficiency.
Differentiated somatic cells can be reprogrammed to totipotent embryos through somatic cell nuclear transfer (SCNT) with low efficiency. The histone deacetylase inhibitor trichostatin A (TSA) has been found to improve SCNT efficiency, but the underlying mechanism remains undetermined. Here, we examined genome-wide H3K9ac during SCNT embryo development and found that aberrant H3K9ac regions resulted in reduced 2-cell genome activation. TSA treatment largely corrects aberrant acetylation in SCNT embryos with an efficiency that is dictated by the native epigenetic environment. We further identified that the overexpression of Dux greatly improves SCNT efficiency by correcting the aberrant H3K9ac signal at its target sites, ensuring appropriate 2-cell genome activation. Intriguingly, the improvement in development mediated by TSA and Kdm4b is impeded by Dux knockout in SCNT embryos. Together, our study reveals that reprogramming of H3K9ac is important for optimal SCNT efficiency and identifies Dux as a crucial transcription factor in this process.
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