BIOPIC, December 21, 2017: In recent years, Professor Fuchou Tang collaborated with Professor Jie Qiao to work on dissecting the DNA methylation reprogramming of human early embryos (Guo et al. 2014, Guo et al. 2015). On December 19, their new discoveries were published in Nature Genetics.  For the first time, the authors interrogated the DNA methylomes of human early embryos at single-cell resolution. They illustrated the balance of demethylation and de novo DNA methylation, as well as methylation divergency between parental genomes during the preimplantation epigenetic reprogramming process.

Figure 1 | DNA methylation reprogramming in human early embryos.

De novo methylation in early embryos

Previous studies reported that the DNA methylation reprogramming is a process of genome-wide DNA demethylation.  However, by recovering more informative cytosines on the genome at single-cell resolution, the authors further showed that there were two waves of de novo methylation occurred from early-pronuclei to mid-pronuclei and 4-cell stage to 8-cell stage respectively. Despite the transient feature of these de novo methylation events, they significantly enriched on transposable elements (TEs), suggesting a potential mechanism of DNA methylation to repress the activity of TEs in order to maintain the genome stability.

Figure 2 | Two waves of de novo methylation

Parental methylation divergency

Although the DNA methylation level of the sperm is much higher than that of oocytes, drastic demethylation occurs upon fertilization on both parental genomes. It is elusive that how parental genomes reprogramming their DNA methylation after the nuclei fused to be one.  By dissecting the heterozygous SNP loci and their linked methylation states, the authors tracked the parental genome methylations during preimplantation development. As a contrary to methylation in sperm and oocytes, the DNA methylation level of the paternal genome is much lower than that of the maternal genome. In other words, the maternal genome inherits much more epigenetic memory through DNA methylation to play more crucial roles in regulation of early development.

Figure 3 | Parental genome DNA methylation dynamics

Lineage tracing by DNA methylation

Notably, the authors illustrated that the genetic lineage of 4-cell blastomeres could be resolved by using DNA methylation alone in both human and mice. The two daughter cells that come from the same mother cell showed more differences in DNA methylation distribution along the genome. This result provides evidences for lineage tracking by using DNA methylation and suggest the potential applications in other biological processes.

Figure 4 | Lineage tracing of 4-cell blastomeres

Dr. Ping Zhu, Dr. Hongshan Guo, Dr. Yu Hou and Dr. Yixi Ren equally contributed to this work, Professor Fuchou Tang, Professor Jie Qiao and Professor Liying Yan were co-corresponding authors. This work is supported by National Natural Science Foundation of China, the National Basic Research Program of China, the Beijing Municipal Science and Technology Commission, the National High-Technology Research and Development Program and the Beijing Advanced Innovation Center for Genomics at Peking University.