Transposable Elements Profiling Reveals DUXA-associated MLT1D Endogenous Retroviral Elements Activation During Bovine Maternal to Zygotic Transition

Transposable elements (TEs) contribute to genomic diversity in mammals, although their regulatory roles in bovines are not well understood. A study analyzed the bovine TE landscape, noting that ruminants contain a substantial proportion (25.6%) of TE-specific elements. The distribution of these elements varies among embryos generated through different methods, such as in vivo fertilization (IVV), in vitro fertilization (IVT), and somatic cell nuclear transfer (SCNT).

Notably, the zygotic genome activation (ZGA) in IVT and SCNT embryos occurs later than in IVV embryos, specifically from the 4-cell stage to the 8-cell stage. SCNT embryos display impaired early transcription initiation at the 4-cell stage and disrupted developmental pathways, including abnormal activation of genes responsible for pluripotency.

Furthermore, a subset of retroviral LTR elements is strongly activated during ZGA in IVV and IVT embryos, whereas this activation is significantly reduced in SCNT embryos. This discrepancy suggests that impaired gene and TE reprogramming may play a role in the developmental defects frequently seen in SCNT embryos. Through epigenomic profiling, the research identified that the MLT1D elements from the ERVL-MaLR LTR family undergo a change in their epigenetic state at ZGA, losing repressive marks and gaining H3K27ac, while also showing enrichment of DUXA-binding motifs.

When DUXA is knocked down in bovine embryos, it leads to a decrease in MLT1D expression and ZGA marker genes. Based on these findings, the study proposes that a subset of DUXA-enriched MLT1D elements act as enhancers, promoting ZGA. The study provides new insights into the regulatory roles of TEs during bovine embryogenesis and lays the groundwork for comparative studies of TE-mediated gene regulation in early mammalian development.