Abstract
Pleomorphic adenoma gene 1 (PLAG1) is a transcription factor that is involved in cancer and growth. We discovered a de novo DNA motif containing a PLAG1 binding site, located within the promoters of genes activated during zygotic genome activation (ZGA) in human embryos. This site frequently overlapped with Alu elements and was conserved in mouse B1 elements. We show that Plag1 is essential for timely preimplantation embryo development. Mouse oocytes lacking maternally loaded Plag1 gave rise to embryos that spent significantly longer time in 2-cell stage, displayed delayed regulation of 1,089 genes and in contrast to wildtype, expressed Plag1 from the paternal allele. The PLAG1 motif was enriched in promoters of mouse delayed-activation genes that also showed a significant overlap with human ZGA genes. By ontology, these mouse and human genes were connected to ribosome biogenesis and protein synthesis. Our data suggests that PLAG1/Plag1 affects ZGA through a conserved DNA motif within retrotransposons influencing ribosomes and protein synthesis, a mechanism that might also explain its roles in cancer and growth.