title: The human PRD-like homeobox gene LEUTX has a central role in embryo genome activation.
abstract: Leucine twenty homeobox (LEUTX) is a paired (PRD)-like homeobox gene that is expressed almost exclusively in human embryos during preimplantation development. We previously identified a novel transcription start site for the predicted human LEUTX gene based on the transcriptional analysis of human preimplantation embryos. The novel variant encodes a protein with a complete homeodomain. Here, we provide a detailed description of the molecular cloning of the complete homeodomain-containing LEUTX Using a human embryonic stem cell overexpression model we show that the complete homeodomain isoform is functional and sufficient to activate the transcription of a large proportion of the genes that are upregulated in human embryo genome activation (EGA), whereas the previously predicted partial homeodomain isoform is largely inactive. Another PRD-like transcription factor, DPRX, is then upregulated as a powerful repressor of transcription. We propose a two-stage model of human EGA in which LEUTX acts as a transcriptional activator at the 4-cell stage, and DPRX as a balancing repressor at the 8-cell stage. We conclude that LEUTX is a candidate regulator of human EGA.
authors: Department of Biosciences and Nutrition, Karolinska Institutet, Novum, Huddinge 141 83, Sweden.
authors: Eeva-Mari
authors: EM
authors: Jouhilahti
authors: Department of Biosciences and Nutrition, Karolinska Institutet, Novum, Huddinge 141 83, Sweden.
authors: Elo
authors: E
authors: Madissoon
authors: Department of Biosciences and Nutrition, Karolinska Institutet, Novum, Huddinge 141 83, Sweden.
authors: Liselotte
authors: L
authors: Vesterlund
authors: Department of Biosciences and Nutrition, Karolinska Institutet, Novum, Huddinge 141 83, Sweden.
authors: Virpi
authors: V
authors: Töhönen
authors: Department of Biosciences and Nutrition, Karolinska Institutet, Novum, Huddinge 141 83, Sweden Competence Centre on Health Technologies, Tartu 50410, Estonia.
authors: Kaarel
authors: K
authors: Krjutškov
authors: Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm 141 86, Sweden.
authors: Alvaro
authors: A
authors: Plaza Reyes
authors: Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm 141 86, Sweden.
authors: Sophie
authors: S
authors: Petropoulos
authors: Center for Hematology and Regenerative Medicine Huddinge, Karolinska Institute, Stockholm 14183, Sweden.
authors: Robert
authors: R
authors: Månsson
authors: Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm 171 77, Sweden.
authors: Sten
authors: S
authors: Linnarsson
authors: Department of Biomedicine, University of Basel, Basel 4058, Switzerland.
authors: Thomas
authors: T
authors: Bürglin
authors: Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm 141 86, Sweden.
authors: Fredrik
authors: F
authors: Lanner
authors: Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm 141 86, Sweden.
authors: Outi
authors: O
authors: Hovatta
authors: Department of Biosciences and Nutrition, Karolinska Institutet, Novum, Huddinge 141 83, Sweden.
authors: Shintaro
authors: S
authors: Katayama
authors: Department of Biosciences and Nutrition, Karolinska Institutet, Novum, Huddinge 141 83, Sweden Science for Life Laboratory, Tomtebodavägen 23 A, Solna 171 21, Sweden Molecular Neurology Research Program, University of Helsinki and Folkhälsan Institute of Genetics, Biomedicum 1, Haartmaninkatu 8, Helsinki 00290, Finland juha.kere@ki.se.
authors: Juha
authors: 0000-0003-1974-0271
authors: J
authors: Kere
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000378:metabolism*; D002460:Cell Line; D024202:Electrophoretic Mobility Shift Assay; D053595:Embryonic Stem Cells / Q000378:metabolism*; D019084:Fluorescent Antibody Technique, Indirect; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D016133:Polymerase Chain Reaction; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*
chemical_list: D018398:Homeodomain Proteins; C000590731:LEUTX protein, human; D020033:Protein Isoforms
keywords: Embryo genome activation; Embryonic stem cells; Homeobox gene; Preimplantation development