Delivering synthetic megabase-scale human DNA into mouse early embryos

De novo epigenomic regulation is complicated by the inherited epigenetic modifications.
The researchers in this study developed SynNICE, a method for assembling and delivering intact, naive, synthetic megabase (Mb)-scale human DNA into early mouse embryos, to study de novo epigenetic regulation.
The authors observed spontaneous incorporation of histones and the establishment of DNA methylation at repeat sequences without H3K9me3 reinforcement at the one-cell stage by delivering a 1.14-Mb human AZFa (hAZFa) locus.
They found out that DNA methylation regulated the transcription of hAZFa initiated at the four-cell stage.
Thus, this study provides a unique platform for exploring de novo epigenomic regulation mechanisms in higher animals.
https://www.nature.com/articles/s41592-025-02746-8
https://sciencemission.com/delivery-of-synthetic-megabase-scale-human-DNA