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

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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

Title: Pleomorphic Adenoma Gene 1 Is Needed For Timely Zygotic Genome Activation and Early Embryo Development
Author: Madissoon, Elo; Damdimopoulos, Anastasios; Katayama, Shintaro; Krjutskov, Kaarel; Einarsdottir, Elisabet; Mamia, Katariina; De Groef, Bert; Hovatta, Outi; Kere, Juha; Damdimopoulou, Pauliina
Contributor: University of Helsinki, CAN-PRO - Translational Cancer Medicine Program
University of Helsinki, Research Programme of Molecular Medicine
University of Helsinki, STEMM - Stem Cells and Metabolism Research Program
Date: 2019-06-10
Number of pages: 11
Belongs to series: Scientific Reports
ISSN: 2045-2322
URI: http://hdl.handle.net/10138/304580
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.
Subject: MOUSE
PACKAGE
PLAG1
3111 Biomedicine
1184 Genetics, developmental biology, physiology
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