title: Characterization and target genes of nine human PRD-like homeobox domain genes expressed exclusively in early embryos.
abstract: PAIRED (PRD)-like homeobox genes belong to a class of predicted transcription factor genes. Several of these PRD-like homeobox genes have been predicted in silico from genomic sequence but until recently had no evidence of transcript expression. We found recently that nine PRD-like homeobox genes, ARGFX, CPHX1, CPHX2, DPRX, DUXA, DUXB, NOBOX, TPRX1 and TPRX2, were expressed in human preimplantation embryos. In the current study we characterized these PRD-like homeobox genes in depth and studied their functions as transcription factors. We cloned multiple transcript variants from human embryos and showed that the expression of these genes is specific to embryos and pluripotent stem cells. Overexpression of the genes in human embryonic stem cells confirmed their roles as transcription factors as either activators (CPHX1, CPHX2, ARGFX) or repressors (DPRX, DUXA, TPRX2) with distinct targets that could be explained by the amino acid sequence in homeodomain. Some PRD-like homeodomain transcription factors had high concordance of target genes and showed enrichment for both developmentally important gene sets and a 36 bp DNA recognition motif implicated in Embryo Genome Activation (EGA). Our data implicate a role for these previously uncharacterized PRD-like homeodomain proteins in the regulation of human embryo genome activation and preimplantation embryo development.
authors.affiliation: Biosciences and Nutrition, Karolinska Institutet, Huddinge, Stockholm, Sweden.
authors.forename: Elo
authors.initials: E
authors.lastname: Madissoon
authors.affiliation: Biosciences and Nutrition, Karolinska Institutet, Huddinge, Stockholm, Sweden.
authors.forename: Eeva-Mari
authors.initials: EM
authors.lastname: Jouhilahti
authors.affiliation: Biosciences and Nutrition, Karolinska Institutet, Huddinge, Stockholm, Sweden.
authors.forename: Liselotte
authors.initials: L
authors.lastname: Vesterlund
authors.affiliation: Biosciences and Nutrition, Karolinska Institutet, Huddinge, Stockholm, Sweden.
authors.forename: Virpi
authors.initials: V
authors.lastname: Töhönen
authors.affiliation: Biosciences and Nutrition, Karolinska Institutet, Huddinge, Stockholm, Sweden.|Competence Centre on Health Technologies, Tartu, Estonia.
authors.forename: Kaarel
authors.initials: K
authors.lastname: Krjutškov
authors.affiliation: Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Huddinge, Stockholm, Sweden.
authors.forename: Sophie
authors.initials: S
authors.lastname: Petropoulos
authors.affiliation: Biosciences and Nutrition, Karolinska Institutet, Huddinge, Stockholm, Sweden.|Molecular Neurology Research Program, University of Helsinki and Folkhälsan Institute of Genetics, Helsinki, Finland.
authors.forename: Elisabet
authors.initials: E
authors.lastname: Einarsdottir
authors.affiliation: Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Sten
authors.initials: S
authors.lastname: Linnarsson
authors.affiliation: Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Huddinge, Stockholm, Sweden.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Lanner
authors.affiliation: Department of Laboratory Medicine, Division of Clinical Immunology, Karolinska Institutet, Huddinge, Stockholm, Sweden.
authors.forename: Robert
authors.initials: R
authors.lastname: Månsson
authors.affiliation: Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Huddinge, Stockholm, Sweden.
authors.forename: Outi
authors.initials: O
authors.lastname: Hovatta
authors.affiliation: Department of Biomedicine, University of Basel, Basel, Switzerland.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Bürglin
authors.affiliation: Biosciences and Nutrition, Karolinska Institutet, Huddinge, Stockholm, Sweden.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Katayama
authors.affiliation: Biosciences and Nutrition, Karolinska Institutet, Huddinge, Stockholm, Sweden.|Molecular Neurology Research Program, University of Helsinki and Folkhälsan Institute of Genetics, Helsinki, Finland.
authors.forename: Juha
authors.initials: J
authors.lastname: Kere
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001755:Blastocyst / Q000378:metabolism*; D003001:Cloning, Molecular; D016384:Consensus Sequence; D018076:DNA, Complementary / Q000235:genetics; D005326:Fetal Proteins / Q000096:biosynthesis / Q000235:genetics*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D015723:Gene Library; D005801:Genes, Homeobox; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics*; D000066449:Human Embryonic Stem Cells / Q000378:metabolism; D006801:Humans; D005810:Multigene Family; D009928:Organ Specificity; D039904:Pluripotent Stem Cells / Q000378:metabolism; D011401:Promoter Regions, Genetic; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D018076:DNA, Complementary; D005326:Fetal Proteins; D018398:Homeodomain Proteins; D014157:Transcription Factors