Chaetocin improves pig cloning efficiency by enhancing epigenetic reprogramming and autophagic activity

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Chaetocin improves pig cloning efficiency by enhancing epigenetic reprogramming and autophagic activity
Pil Soo Jeong; Bo Woong Sim; Soo-Hyun Park; Min Ju Kim; Hyo-Gu Kang; T Nanjidsuren; Sanghoon Lee; Bong-Seok Song; D B Koo; Sun-Uk Kim
Bibliographic Citation
International Journal of Molecular Sciences, vol. 21, no. 14, pp. 4836-4836
Publication Year
Efficient epigenetic reprogramming is crucial for the in vitro development of mammalian somatic cell nuclear transfer (SCNT) embryos. The aberrant levels of histone H3 lysine 9 trimethylation (H3K9me3) is an epigenetic barrier. In this study, we evaluated the effects of chaetocin, an H3K9me3-specific methyltransferase inhibitor, on the epigenetic reprogramming and developmental competence of porcine SCNT embryos. The SCNT embryos showed abnormal levels of H3K9me3 at the pronuclear, two-cell, and four-cell stages compared to in vitro fertilized embryos. Moreover, the expression levels of H3K9me3-specific methyltransferases (suv39h1 and suv39h2) and DNA methyltransferases (DNMT1, DNMT3a, and DNMT3b) were higher in SCNT embryos. Treatment with 0.5 nM chaetocin for 24 h after activation significantly increased the developmental competence of SCNT embryos in terms of the cleavage rate, blastocyst formation rate, hatching rate, cell number, expression of pluripotency-related genes, and cell survival rate. In particular, chaetocin enhanced epigenetic reprogramming by reducing the H3K9me3 and 5-methylcytosine levels and restoring the abnormal expression of H3K9me3-specific methyltransferases and DNA methyltransferases. Chaetocin induced autophagic activity, leading to a significant reduction in maternal mRNA levels in embryos at the pronuclear and two-cell stages. These findings revealed that chaetocin enhanced the developmental competence of porcine SCNT embryos by regulating epigenetic reprogramming and autophagic activity and so could be used to enhance the production of transgenic pigs for biomedical research.
chaetocinepigenetic reprogrammingH3K9me3DNA methylationporcine SCNT embryoautophagy
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Ochang Branch Institute > Division of Bioinfrastructure > Futuristic Animal Resource & Research Center > 1. Journal Articles
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