DNA methylation dynamics during zygotic genome activation in goat

Abstract

DNA methylation is a crucial element in the epigenetic regulation of mammalian embryonic development. However, the subtle changes in DNA methylation differ in species, and, little information is known regarding the dynamics of DNA methylation at the single-base resolution in goat. In the present study, we studied the DNA methylation dynamics during goat zygotic genome activation (ZGA) at global and single-base resolution using immunostaining and reduced representation bisulfite sequencing, respectively. We showed that DNA methylation was decreased both at global and single-base resolution, and the expression of TET1 was increased while DNMT1 was decreased during ZGA in goat. We identified 51058 tiles of differential methylation regions (DMRs), which were enriched in the developmental process, the regulation of developmental process, AMPK signaling pathway, mTOR signaling pathway, autophagy, and lysosome, as revealed by GO and KEGG enrichment analysis. Furthermore, we found an association between the methylation level and the expression of imprinted genes (IGF2R, PEG3, and ZFP64), maternal genes (TRIM28, SETD1A, SIN3A, and NPM2), and zygotic genes (DUXA, IGF2BP1, WT1, and ZIM3), suggesting that DNA methylation is in the tight control of ZGA in goat by regulating the expression of the critical genes. Our data will help to understand the stochastic ZGA events to achieve better development of goat embryos in vitro and provide an excellent source for further ZGA studies.