Effects of histone methyltransferase inhibitor chaetocin on histone H3K9 methylation of cultured ovine somatic cells and development of preimplantation cloned embryos.

Aberrant hypermethylation of histone H3 lysine 9 (H3K9) is a key barrier to the development of cloned embryos by somatic cell nuclear transfer (SCNT). The objective of this study was to assess the effects of chaetocin, an inhibitor of H3K9 methyltransferase SUV39 H, in regulating the H3K9 methylation in ovine SCNT embryos. Treatment of sheep fetal fibroblast cells with chaetocin specifically decreased the levels of H3K9 di-and trimethylation, and down-regulated the expression of H3K9 methyltransferases, SUV39H1/2 and G9A. Cloned embryos from chaetocin-treated cells could develop to the blastocyst stage at a similar rate to those derived from non-treated cells. However, direct treatment of SCNT or in vitro fertilized embryos with chaetocin impaired the embryonic development. These results suggest that although chaetocin is a potential agent for modulating H3K9 methylation in cells, it may have an adverse effect on the development of embryos.