Rabbit Anti-Mouse Kdm6b Polyclonal Antibody

Despite the success of animal cloning by somatic cell nuclear transfer (SCNT) in many species, the method is limited by its low efficiency. After zygotic genome activation (ZGA) during mouse development, a large number of endogenous retroviruses (ERVs) are expressed, including the murine endogenous retrovirus-L (MuERVL/MERVL). In this study, we generate a series of MERVL reporter mouse strains to detect the ZGA event in embryos. We show that the majority of SCNT embryos do not undergo ZGA, and H3K27me3 prevents SCNT reprogramming. Overexpression of the H3K27me3-specific demethylase KDM6A, but not of KDM6B, improves the efficiency of SCNT. Conversely, knockdown of KDM6B not only facilitates ZGA, but also impedes ectopic Xist expression in SCNT reprogramming. Furthermore, knockdown of KDM6B increases the rate of SCNT-derived embryonic stem cells from Duchenne muscular dystrophy embryos. These results not only provide insight into the mechanisms underlying failures of SCNT, but also may extend the applications of SCNT.

Aberrant epigenetic reprogramming occurs frequently in the development of tumors. Histone H3 lysine 27 trimethylation (H3K27me3) exerts a repressive epigenetic mark on a large number of genes. UTX and JMJD3 are the only two histone demethylases which activate gene expression via demethylating H3K27me3 to H3K27me2 or H3K27me1. Current studies show that dysregulation of these two proteins are heavily linked to oncogenesis in various tissue types. Accumulating evidence suggested that there is remarkable therapeutic potential of targeting JMJD3 or UTX in different types of cancer. Herein, we shall give a brief review on the functional roles of JMJD3 and UTX in cancers and evaluate the available compounds and agents targeting UTX and JMJD3. Finally, we also discuss the several modalities that target UTX and JMJD3 for cancer therapy. This review will help to develop novel strategies to abolish or restore effects of UTX and JMJD3 in the pathogenesis of cancer.