Combined Chaetocin/Trichostatin A Treatment Improves the Epigenetic Modification and Developmental Competence of Porcine Somatic Cell Nuclear Transfer Embryos

Frontiers in Cell and Developmental Biology

Hyo-Gu Kang¹  Ye Eun Joo²  Soo-Hyun Park²  Min Ju Kim²  Min Ah Gwon³  Pil-Soo Jeong³  Deog-Bon Koo³  Sun-Uk Kim⁴  Bo-Woong Sim⁵  Bong-Seok Song⁵  Hae-Jun Yang⁵  Young-Ho Park⁵  Sanghoon Lee⁵ 

[1] Department of Animal Science and Biotechnology, College of Agriculture and Life Science, Chungnam National University, Daejeon, South Korea;Department of Animal Science, College of Natural Resources and Life Science, Pusan National University, Miryang, South Korea;Department of Biotechnology, College of Engineering, Daegu University, Gyeongsan, South Korea;Department of Functional Genomics, University of Science and Technology, Daejeon, South Korea;Futuristic Animal Resource and Research Center (FARRC), Korea Research Institute of Bioscience and Biotechnology (KRIBB), Cheongju, South Korea;

关键词: chaetocin;    trichostatin A (TSA);    somatic cell nuclear transfer (SCNT);    porcine embryonic development;    epigenetic reprogramming;    zygotic genome activation;   

DOI  :  10.3389/fcell.2021.709574

来源: DOAJ

【 摘 要 】

Developmental defects in somatic cell nuclear transfer (SCNT) embryos are principally attributable to incomplete epigenetic reprogramming. Small-molecule inhibitors such as histone methyltransferase inhibitors (HMTi) and histone deacetylase inhibitors (HDACi) have been used to improve reprogramming efficiency of SCNT embryos. However, their possible synergistic effect on epigenetic reprogramming has not been studied. In this study, we explored whether combined treatment with an HMTi (chaetocin) and an HDACi (trichostatin A; TSA) synergistically enhanced epigenetic reprogramming and the developmental competence of porcine SCNT embryos. Chaetocin, TSA, and the combination significantly increased the cleavage and blastocyst formation rate, hatching/hatched blastocyst rate, and cell numbers and survival rate compared to control embryos. In particular, the combined treatment improved the rate of development to blastocysts more so than chaetocin or TSA alone. TSA and combined chaetocin/TSA significantly reduced the H3K9me3 levels and increased the H3K9ac levels in SCNT embryos, although chaetocin alone significantly reduced only the H3K9me3 levels. Moreover, these inhibitors also decreased global DNA methylation in SCNT embryos. In addition, the expression of zygotic genome activation- and imprinting-related genes was increased by chaetocin or TSA, and more so by the combination, to levels similar to those of in vitro-fertilized embryos. These results suggest that combined chaetocin/TSA have synergistic effects on improving the developmental competences by regulating epigenetic reprogramming and correcting developmental potential-related gene expression in porcine SCNT embryos. Therefore, these strategies may contribute to the generation of transgenic pigs for biomedical research.

【 授权许可】

Unknown