GSE111035
Maternal Plag1 deficiency delays two-cell stage embryo development and embryonic genome activation [Uterus]
Pleomorphic adenoma gene 1 (PLAG1) encodes a transcription factor involved in cancer and growth. We study the role of PLAG1 in female reproductive tract and preimplantation embryos using STRT RNA-seq of single embryos from wild type and knockout mothers (both mated with wild type studs). We did not find significant effects in ovaries or uterus. The lack of maternal Plag1 led to delayed mouse 2-cell stage embryo development, compensatory expression of Plag1 from the paternal allele, and dysregulation of 1,089 genes. Half of these genes displayed a pattern of delayed activation and play roles in ribosome biogenesis and protein synthesis. These mouse genes further showed a significant overlap with human EGA genes with similar ontology, and an enrichment of the PLAG1 de novo motif. We conclude that Plag1 affects EGA through retrotransposons influencing ribosomes and protein synthesis, a mechanism that might also explain its roles in cancer and growth Overall design: Uterus was dissected from 8 WT and 8 Plag1KO mice that were used in superovulation experiments and used for RNA-seq. One uterine horn was split longitudinally and mucosa exposed. The endometrial cells were scraped with a scalpel. Endometrial cells (ENDO), remaining myometrium (MYO), and a piece of intact uterine horn were transferred to RNA later.