Down-Regulation of H3K4me3 by MM-102 Facilitates Epigenetic Reprogramming of Porcine Somatic Cell Nuclear Transfer Embryos

Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology
Zhiren ZhangZiyi Li

Abstract

Aberrantly high levels of H3K4me3, caused by incomplete epigenetic reprogramming, likely cause a low efficiency of somatic cell nuclear transfer (SCNT). Smal molecule inhibitors aimed at epigenetic modification can be used to improve porcine SCNT embryo development. In this study, we examined the effects of MM-102, an H3K4 histone methyltransferase inhibitor, on porcine SCNT preimplantation embryos to investigate the mechanism by which H3K4 methylation regulated global epigenetic reprograming during SCNT. MM-102 was added to the SCNT embryos culture system and the global levels of various epigenetic modifications were measured by immunofluorescence (IF) staining and were quantified by Image J software. Relative genes expression levels were detected by quantitative real-time PCR. MM-102 (75 μM) treatment reduced global H3K4, H3K9 methylation and 5mC levels especially at the zygotic gene activation (ZGA) and blastocyst stages. MM-102 treatment mainly down-regulated a series of DNA and histone methyltransferases, and up-regulated a number of hitone acetyltransferases and transcriptional activators. Furthermore, MM-102 treatment positively regulated the mRNA expression of genes related to pluripotency (OCT4, NANOG, CDX2) and apopto...Continue Reading

Citations

May 9, 2018·Stem Cells and Development·Elena Gonzalez-Munoz, Jose B Cibelli
Jun 21, 2019·Epigenetics : Official Journal of the DNA Methylation Society·Vitor Braga RissiVilceu Bordignon
Aug 9, 2019·Cellular Reprogramming·Xingwang WangZicong Li
Jan 10, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Chuan ZhouYong Zhang
Jul 12, 2020·International Journal of Molecular Sciences·Pil-Soo JeongSun-Uk Kim
Sep 4, 2019·Molecular Reproduction and Development·Caroline G LucasTiago Collares
Mar 20, 2021·Molecular Therapy. Nucleic Acids·Mingtian DengFeng Wang
Jun 29, 2021·Zygote : the Biology of Gametes and Early Embryos·Jongki ChoChung-Gyu Park
Sep 30, 2021·Cell Cycle·Deling JiaoHong-Jiang Wei
Oct 14, 2021·Nature Communications·Zhongxing SunDong Fang

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