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

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dc.contributor University of Helsinki, CAN-PRO - Translational Cancer Medicine Program en
dc.contributor University of Helsinki, Research Programme of Molecular Medicine en
dc.contributor University of Helsinki, STEMM - Stem Cells and Metabolism Research Program en
dc.contributor.author Madissoon, Elo
dc.contributor.author Damdimopoulos, Anastasios
dc.contributor.author Katayama, Shintaro
dc.contributor.author Krjutskov, Kaarel
dc.contributor.author Einarsdottir, Elisabet
dc.contributor.author Mamia, Katariina
dc.contributor.author De Groef, Bert
dc.contributor.author Hovatta, Outi
dc.contributor.author Kere, Juha
dc.contributor.author Damdimopoulou, Pauliina
dc.date.accessioned 2019-08-14T09:32:01Z
dc.date.available 2019-08-14T09:32:01Z
dc.date.issued 2019-06-10
dc.identifier.citation Madissoon , E , Damdimopoulos , A , Katayama , S , Krjutskov , K , Einarsdottir , E , Mamia , K , De Groef , B , Hovatta , O , Kere , J & Damdimopoulou , P 2019 , ' Pleomorphic Adenoma Gene 1 Is Needed For Timely Zygotic Genome Activation and Early Embryo Development ' , Scientific Reports , vol. 9 , 8411 . https://doi.org/10.1038/s41598-019-44882-0 en
dc.identifier.issn 2045-2322
dc.identifier.other PURE: 126120355
dc.identifier.other PURE UUID: 0bf65619-afe0-47c4-9a51-9148980c1513
dc.identifier.other WOS: 000470847700008
dc.identifier.uri http://hdl.handle.net/10138/304580
dc.description.abstract 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. en
dc.format.extent 11
dc.language.iso eng
dc.relation.ispartof Scientific Reports
dc.rights en
dc.subject MOUSE en
dc.subject PACKAGE en
dc.subject PLAG1 en
dc.subject 3111 Biomedicine en
dc.subject 1184 Genetics, developmental biology, physiology en
dc.title Pleomorphic Adenoma Gene 1 Is Needed For Timely Zygotic Genome Activation and Early Embryo Development en
dc.type Article
dc.description.version Peer reviewed
dc.identifier.doi https://doi.org/10.1038/s41598-019-44882-0
dc.type.uri info:eu-repo/semantics/other
dc.type.uri info:eu-repo/semantics/publishedVersion
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