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Effects of the Histone Methyltransferase Inhibitor UNC 0638 on Histone H3K9 Dimethylation of Cultured Ovine Somatic Cells and Development of Resulting Early Cloned Embryos
Author(s) -
Fu L,
Yan FX,
An XR,
Hou J
Publication year - 2014
Publication title -
reproduction in domestic animals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.546
H-Index - 66
eISSN - 1439-0531
pISSN - 0936-6768
DOI - 10.1111/rda.12277
Subject(s) - histone methyltransferase , histone , methyltransferase , histone h3 , embryo , biology , epigenetics , somatic cell , histone methylation , microbiology and biotechnology , methylation , dna methylation , biochemistry , dna , gene , gene expression
Contents Aberrant hypermethylation of histone H3 lysine 9 (H3K9) may be involved in the developmental failure of cloned embryos. UNC 0638 is a type of small molecule that can specifically inhibit the enzyme activity of histone methyltransferase EHMT 2 and reduce the H3K9 dimethylation (H3K9me2) levels in cells. The objective of this study was to investigate the effect of UNC 0638 in regulating H3K9me2 and development of cloned embryos. Results showed that UNC 0638 could efficiently reduce H3K9me2 levels of cultured sheep foetal fibroblast cells in a concentration‐dependent manner. Cloned embryos were subsequently produced from UNC 0638‐treated donor cells with down‐regulated H3K9me2, but their in vitro development was not improved when compared with the control. Our study suggested that revision of the single histone H3K9me2 modification may be not sufficient for rescuing the development of cloned embryos. However, because of its low cellular toxicity, UNC 0638 may still be a potential chemical that could be used in regulating epigenetic modification of cloned embryos.