title: The serine 106 residue within the N-terminal transactivation domain is crucial for Oct4 function in mice.
abstract: Pou5f1/Oct4 is a key transcription factor for the induction of pluripotency and totipotency in preimplantation mouse embryos. In mice, loss or gain of function experiments have demonstrated an important role for Oct4 in preimplantation and developmental ability. In this study, using mouse preimplantation embryos as a model for the evaluation of Oct4 function, we constructed Oct4 overexpression embryos with various mutations at the N-terminal transactivation domain. Developmental competency and molecular biological phenotypes depended on the type of mutation. The replacement of serine 106 with alanine resulted in more severe phenotypes similar to that of wild type Oct4, indicating that this alteration using alanine is negligible for Oct4 function. In contrast, we found that Oct4-specific antibodies could not recognize Oct4 protein when this residue was replaced by aspartic acid (Oct4-S106D). Oct4-S106D overexpressing embryos did not show developmental arrest and aberrant chromatin structure. Thus, these results demonstrated that the Ser-106 residue within the N-terminal transactivation domain is crucial for Oct4 function and suggested that this mutation might affect Oct4 protein conformation.
authors.affiliation: Center for Regenerative Medicine,National Research Institute for Child Health and Development,2-10-1 Okura,Setagaya,Tokyo 157-8535,Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Mitani
authors.affiliation: Center for Regenerative Medicine,National Research Institute for Child Health and Development,2-10-1 Okura,Setagaya,Tokyo 157-8535,Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Fukuda
authors.affiliation: Department of Molecular Genetics,Kitasato University Graduate School of Medical Sciences,1-15-1 Kitasato,Minami,Sagamihara,Kanagawa 252-0374,Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Miyashita
authors.affiliation: Center for Regenerative Medicine,National Research Institute for Child Health and Development,2-10-1 Okura,Setagaya,Tokyo 157-8535,Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Umezawa
authors.affiliation: Center for Regenerative Medicine,National Research Institute for Child Health and Development,2-10-1 Okura,Setagaya,Tokyo 157-8535,Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Akutsu
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000166:cytology* / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology* / Q000378:metabolism; D005260:Female; D005307:Fertilization in Vitro; D018507:Gene Expression Regulation, Developmental; D008297:Male; D051379:Mice; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism*; D000072417:Protein Domains; D012694:Serine / Q000737:chemistry* / Q000235:genetics; D015533:Transcriptional Activation
chemical_list: D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D012694:Serine
keywords: Embryonic development; Heterochromatin; Mutagenesis; Oct4; Preimplantation