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Pleomorphic adenoma gene 1 (PLAG1) is a transcription factor involved in cancer and growth. We discovered a  de novo  DNA motif containing a PLAG1 binding site in the promoters of genes activated during zygotic genome activation (ZGA) in human embryos. This motif was located within an Alu element in a region that was conserved in the murine B1 element. We show that maternally provided  Plag1  is needed for timely mouse preimplantation embryo development. Heterozygous mouse embryos lacking maternal  Plag1  showed disrupted regulation of 1,089 genes, spent significantly longer time in the 2-cell stage, and started expressing  Plag1  ectopically from the paternal allele. The  de novo  PLAG1 motif was enriched in the promoters of the genes whose activation was delayed in the absence of  Plag1 . Further, these mouse genes showed a significant overlap with genes upregulated during human ZGA that also contain the motif. By gene ontology, the mouse and human ZGA genes with  de novo  PLAG1 motifs were involved in ribosome biogenesis and protein synthesis. Collectively, our data suggest that PLAG1 affects embryo development in mice and humans through a conserved DNA motif within Alu/B1 elements located in the promoters of a subset of ZGA genes.

Pleomorphic Adenoma Gene 1 Is Needed For Timely Zygotic Genome Activation and Early Embryo Development