Despite the success in generating animals through somatic cell nuclear transfer(SCNT)in many different species,a common problem associated with SCNT is the low efficiency.When zygotic(or embryonic)genome activation(ZGA or EGA),a large number of endogenous retroviruses(ERVs)are expressed,including the murine endogenous retrovirus-L(MuERVL/MERVL).Here,we generated a series of MERVLreporter mouse stains,which allows us to detect the ZGA of SCNT embryos.We found the majority of SCNT embryos are ZGA failure,and histone H3 lysine 27 trimethylation(H3K27me3)as a barrier preventing SCNT reprogramming.Overexpression of the H3K27me3 specific demethylases KDM6A rather than KDM6B improves the efficiency of SCNT.However,knock-down KDM6B also facilitates ZGA and consequently improves the SCNT reprogramming.We also revealed that knock-down KDM6B increased the rate of SCNTderived Duchenne Muscular Dystrophy(DMD)embryonic stem cells establishment.