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

Abstract

Transposable elements (TEs) are a major source of genomic diversity in mammals, yet their regulatory roles in the bovine genome remain poorly understood. Through characterizing bovine TE landscape, despite the substantial proportion (25.6%) of ruminant-specific TEs, we observe age- and class-dependent genomic distribution patterns similar to those observed in other mammals. Next, we profile TE and gene expression dynamics in pre-implantation embryos generated in vivo (IVV), by in vitro fertilization (IVT), and through somatic cell nuclear transfer (SCNT). The zygotic genome activation (ZGA) is shifted from the 4-cell stage to the 8-cell stage in IVT and SCNT embryos compared to IVV embryos. SCNT embryos exhibit impaired initiation of early transcription programs at the 4-cell stage and disrupted developmental trajectories, including abnormal activation of pluripotency-associated genes. A subset of retroviral LTR elements are strongly activated at ZGA in IVV and IVT embryos, whereas their activation is markedly muted in SCNT embryos, suggesting that impaired gene and TE reprogramming may contribute to the developmental defects commonly observed in SCNT embryos. By epigenomic profiling, the MLT1D elements from the ERVL-MaLR LTR family lose repressive marks and gain H3K27ac at ZGA, together with DUXA-binding motif enrichment. Knockdown of DUXA in bovine embryos significantly reduced MLT1D expression and ZGA marker genes. We propose that a subset of DUXA-enriched MLT1D functions as enhancers that promote ZGA. Overall, our study provides new insights into the regulatory roles of TEs during bovine embryogenesis and establishes a framework for comparative studies of TE-mediated gene regulation in early mammalian development.