A Novel SINE Transposable Element-Associated lncRNA Regulates Zygotic Genome Activation in Porcine Parthenogenetically Activated Embryos

Abstract

Zygotic genome activation (ZGA) is a pivotal event during early mammalian embryonic development and is regulated by multiple molecular factors. In mice, previous studies have demonstrated that long non-coding RNAs (lncRNAs) and transposable elements (TEs) participate in the regulation of this process. However, the functional roles of TEs-associated lncRNAs in porcine ZGA remain largely unknown. In this study, we identified a previously unannotated lncRNA associated with a SINE transposable element sequence in porcine parthenogenetically activated embryos, which we named LincSAKP. LincSAKP exhibited peak expression at the 8-cell stage, coinciding with ZGA, was predominantly localized in the nucleus, and lacked protein-coding potential. Functional analyses demonstrated that depletion of LincSAKP resulted in developmental arrest at the 8-cell stage, accompanied by reduced chromatin accessibility, impaired nascent transcription, and aberrant expression of multiple ZGA marker genes and transcription factors. Transcriptomic analysis combined with rescue experiments identified EP300 as a critical downstream target of LincSAKP. Notably, Depletion of either LincSAKP or EP300 impairs histone H3K27ac modification. EP300 overexpression effectively alleviated the developmental defects caused by LincSAKP depletion. Collectively, our findings identify EP300 as a downstream mediator of LincSAKP in regulating zygotic genome activation, providing insights into the functional network of SINE-associated lncRNAs during parthenogenetically activated early embryonic development. This study expands our understanding of the functional roles of TE-associated non-coding RNAs in early embryonic development and provides a potential theoretical basis for improving the efficiency of in vitro culture of porcine embryos.