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.

分化的体细胞可以通过体细胞核移植（SCNT）低效率地重新编程为全能胚胎。已发现组蛋白脱乙酰基酶抑制剂曲古抑菌素A（TSA）可以提高SCNT的效率，但其潜在机制仍不确定。在这里，我们检查了SCNT胚胎发育过程中全基因组的H3K9ac，发现异常的H3K9ac区导致减少的2细胞基因组激活。TSA处理在很大程度上纠正了SCNT胚胎中异常的乙酰化，其效率取决于天然表观遗传环境。我们进一步发现，Dux的过表达通过纠正其靶位点异常的H3K9ac信号，从而确保适当的2细胞基因组激活，大大提高了SCNT效率。有趣的是，由TSA和KDM4B被阻止通过的DUX在SCNT胚胎淘汰赛。总之，我们的研究表明H3K9ac的重编程对于最佳SCNT效率非常重要，并确定Dux是此过程中的关键转录因子。