Inhibiting repressive epigenetic modification promotes telomere rejuvenation in somatic cell reprogramming

The efficiency of somatic cell nuclear transfer (SCNT) reprogramming is extremely low in terms of production of cloned animals. Here, we found that telomere rejuvenation is a critical event for SCNT reprogramming. Through small‐molecule screening, we identified that melatonin significantly improved the in vitro and in vivo developmental competence of SCNT‐derived embryos. Through use of embryonic biopsy, single‐cell RNA sequencing, and quantitative FISH experiments, we revealed that melatonin not only attenuated the zygotic genome activation defect but also facilitated telomere elongation in the SCNT embryos. Further investigation indicated that melatonin inhibited heterochromatic epigenetic modification related to gene silencing including DNA methylation and histone H3 lysine 9 trimethylation. In addition, melatonin could increase the level of activation markers such as acetylated histone H3. This is the first study to characterize melatonin‐treatment and telomere rejuvenation in SCNT‐mediated reprogramming. Moreover, combinational use of melatonin‐treated donor embryos and pseudopregnant recipients achieved synergistic enhancement of the production of cloned animals.—Yang, L., Liu, X., Song, L., Su, G., Di, A., Bai, C., Wei, Z., Li, G. Inhibiting repressive epigenetic modification promotes telomere rejuvenation in somatic cell reprogramming. FASEB J. 33, 13982‐13997 (2019). www.fasebj.org