Methylation reprogramming during mammalian development is conserved across species, but cloned embryos show aberrant reprogramming. In normal embryos, the paternal genome undergoes genome-wide demethylation early in development, followed by remethylation. In cloned embryos, however, demethylation is incomplete, and de novo methylation occurs prematurely, leading to abnormal methylation patterns resembling those of differentiated cells. Cloned embryos exhibit reduced methylation in early stages but then show premature de novo methylation, resulting in highly methylated nuclei similar to donor fibroblasts. This aberrant reprogramming may contribute to the low efficiency of cloning. DNA methylation in mammals primarily occurs at CpG dinucleotides and plays key roles in imprinting, X chromosome inactivation, and gene silencing. In mice, mutations in Dnmt1, Dnmt3a, and Dnmt3b lead to genome-wide demethylation and lethality. Methylation patterns in somatic cells are generally stable, but in mice, two developmental periods involve global reprogramming. These include demethylation in primordial germ cells and preimplantation embryos. In preimplantation embryos, the paternal genome is demethylated, while the maternal genome undergoes stepwise demethylation. This results in undermethylation in morulae, followed by de novo methylation in the blastocyst. In cloned embryos, the somatic donor nucleus is not fully reprogrammed, leading to premature de novo methylation and nuclear reorganization. This results in highly methylated nuclei in cloned morulae, similar to donor fibroblasts. The study shows that epigenetic reprogramming is aberrant in most cloned embryos, which may explain the low success rate of cloning. The findings suggest that correct epigenetic reprogramming is essential for successful development. The study also highlights the importance of understanding the mechanisms of methylation reprogramming in mammals, as it has implications for cloning and developmental biology.Methylation reprogramming during mammalian development is conserved across species, but cloned embryos show aberrant reprogramming. In normal embryos, the paternal genome undergoes genome-wide demethylation early in development, followed by remethylation. In cloned embryos, however, demethylation is incomplete, and de novo methylation occurs prematurely, leading to abnormal methylation patterns resembling those of differentiated cells. Cloned embryos exhibit reduced methylation in early stages but then show premature de novo methylation, resulting in highly methylated nuclei similar to donor fibroblasts. This aberrant reprogramming may contribute to the low efficiency of cloning. DNA methylation in mammals primarily occurs at CpG dinucleotides and plays key roles in imprinting, X chromosome inactivation, and gene silencing. In mice, mutations in Dnmt1, Dnmt3a, and Dnmt3b lead to genome-wide demethylation and lethality. Methylation patterns in somatic cells are generally stable, but in mice, two developmental periods involve global reprogramming. These include demethylation in primordial germ cells and preimplantation embryos. In preimplantation embryos, the paternal genome is demethylated, while the maternal genome undergoes stepwise demethylation. This results in undermethylation in morulae, followed by de novo methylation in the blastocyst. In cloned embryos, the somatic donor nucleus is not fully reprogrammed, leading to premature de novo methylation and nuclear reorganization. This results in highly methylated nuclei in cloned morulae, similar to donor fibroblasts. The study shows that epigenetic reprogramming is aberrant in most cloned embryos, which may explain the low success rate of cloning. The findings suggest that correct epigenetic reprogramming is essential for successful development. The study also highlights the importance of understanding the mechanisms of methylation reprogramming in mammals, as it has implications for cloning and developmental biology.