title: Androgen Regulates Mafb Expression Through its 3'UTR During Mouse Urethral Masculinization.
abstract: External genitalia are prominent organs showing hormone-dependent sexual differentiation. Androgen is an essential regulator of masculinization of the genital tubercle, which is the anlage of external genitalia. We have previously shown that v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog B (MAFB) is an androgen-inducible regulator of embryonic urethral masculinization in mice. However, it remains unclear how androgen regulates Mafb expression. The current study suggests that the Mafb 3' untranslated region (UTR) is an essential region for its regulation by androgen. We identified 2 functional androgen response elements (AREs) in Mafb 3'UTR. Androgen receptor is bound to such AREs in 3'UTR during urethral masculinization. In addition to 3'UTR, Mafb 5'UTR also showed androgen responsiveness. Moreover, we also demonstrated that β-catenin, one of genital tubercle masculinization factors, may be an additional regulator of Mafb expression during urethral masculinization. This study provides insights to elucidate mechanisms of gene regulation through AREs present in Mafb 3'UTR for a better understanding of the processes of urethral masculinization.
authors.affiliation: Department of Developmental Genetics (S.M., K.S., G.Y.), Institute of Advanced Medicine, Wakayama Medical University, Wakayama 641-8509, Japan; Okazaki Institute for Integrative Bioscience (Y.O.), National Institute for Basic Biology, National Institutes of Natural Sciences, The Graduate University for Advanced Studies (SOKENDAI), Okazaki, Aichi 444-8787, Japan; Department of Medical Cell Biology (S.H.), Institute of Molecular Embryology and Genetics, Kumamoto University, Chuo-ku, Kumamoto 860-0811, Japan; Division of Bioinformatics (T.S., M.S.), Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan; Institute of Biomedical Sciences (T.M.), University of Tokushima Graduate School, Tokushima 770-8503, Japan; Venetian Institute of Molecular Medicine (A.O.), 35129 Padua, Italy; and Department of Anti-Aging Medicine (S.I.), Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan.
authors.forename: Shoko
authors.initials: S
authors.lastname: Matsushita
authors.affiliation: Department of Developmental Genetics (S.M., K.S., G.Y.), Institute of Advanced Medicine, Wakayama Medical University, Wakayama 641-8509, Japan; Okazaki Institute for Integrative Bioscience (Y.O.), National Institute for Basic Biology, National Institutes of Natural Sciences, The Graduate University for Advanced Studies (SOKENDAI), Okazaki, Aichi 444-8787, Japan; Department of Medical Cell Biology (S.H.), Institute of Molecular Embryology and Genetics, Kumamoto University, Chuo-ku, Kumamoto 860-0811, Japan; Division of Bioinformatics (T.S., M.S.), Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan; Institute of Biomedical Sciences (T.M.), University of Tokushima Graduate School, Tokushima 770-8503, Japan; Venetian Institute of Molecular Medicine (A.O.), 35129 Padua, Italy; and Department of Anti-Aging Medicine (S.I.), Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Suzuki
authors.affiliation: Department of Developmental Genetics (S.M., K.S., G.Y.), Institute of Advanced Medicine, Wakayama Medical University, Wakayama 641-8509, Japan; Okazaki Institute for Integrative Bioscience (Y.O.), National Institute for Basic Biology, National Institutes of Natural Sciences, The Graduate University for Advanced Studies (SOKENDAI), Okazaki, Aichi 444-8787, Japan; Department of Medical Cell Biology (S.H.), Institute of Molecular Embryology and Genetics, Kumamoto University, Chuo-ku, Kumamoto 860-0811, Japan; Division of Bioinformatics (T.S., M.S.), Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan; Institute of Biomedical Sciences (T.M.), University of Tokushima Graduate School, Tokushima 770-8503, Japan; Venetian Institute of Molecular Medicine (A.O.), 35129 Padua, Italy; and Department of Anti-Aging Medicine (S.I.), Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Ogino
authors.affiliation: Department of Developmental Genetics (S.M., K.S., G.Y.), Institute of Advanced Medicine, Wakayama Medical University, Wakayama 641-8509, Japan; Okazaki Institute for Integrative Bioscience (Y.O.), National Institute for Basic Biology, National Institutes of Natural Sciences, The Graduate University for Advanced Studies (SOKENDAI), Okazaki, Aichi 444-8787, Japan; Department of Medical Cell Biology (S.H.), Institute of Molecular Embryology and Genetics, Kumamoto University, Chuo-ku, Kumamoto 860-0811, Japan; Division of Bioinformatics (T.S., M.S.), Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan; Institute of Biomedical Sciences (T.M.), University of Tokushima Graduate School, Tokushima 770-8503, Japan; Venetian Institute of Molecular Medicine (A.O.), 35129 Padua, Italy; and Department of Anti-Aging Medicine (S.I.), Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan.
authors.forename: Shinjiro
authors.initials: S
authors.lastname: Hino
authors.affiliation: Department of Developmental Genetics (S.M., K.S., G.Y.), Institute of Advanced Medicine, Wakayama Medical University, Wakayama 641-8509, Japan; Okazaki Institute for Integrative Bioscience (Y.O.), National Institute for Basic Biology, National Institutes of Natural Sciences, The Graduate University for Advanced Studies (SOKENDAI), Okazaki, Aichi 444-8787, Japan; Department of Medical Cell Biology (S.H.), Institute of Molecular Embryology and Genetics, Kumamoto University, Chuo-ku, Kumamoto 860-0811, Japan; Division of Bioinformatics (T.S., M.S.), Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan; Institute of Biomedical Sciences (T.M.), University of Tokushima Graduate School, Tokushima 770-8503, Japan; Venetian Institute of Molecular Medicine (A.O.), 35129 Padua, Italy; and Department of Anti-Aging Medicine (S.I.), Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Sato
authors.affiliation: Department of Developmental Genetics (S.M., K.S., G.Y.), Institute of Advanced Medicine, Wakayama Medical University, Wakayama 641-8509, Japan; Okazaki Institute for Integrative Bioscience (Y.O.), National Institute for Basic Biology, National Institutes of Natural Sciences, The Graduate University for Advanced Studies (SOKENDAI), Okazaki, Aichi 444-8787, Japan; Department of Medical Cell Biology (S.H.), Institute of Molecular Embryology and Genetics, Kumamoto University, Chuo-ku, Kumamoto 860-0811, Japan; Division of Bioinformatics (T.S., M.S.), Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan; Institute of Biomedical Sciences (T.M.), University of Tokushima Graduate School, Tokushima 770-8503, Japan; Venetian Institute of Molecular Medicine (A.O.), 35129 Padua, Italy; and Department of Anti-Aging Medicine (S.I.), Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan.
authors.forename: Mikita
authors.initials: M
authors.lastname: Suyama
authors.affiliation: Department of Developmental Genetics (S.M., K.S., G.Y.), Institute of Advanced Medicine, Wakayama Medical University, Wakayama 641-8509, Japan; Okazaki Institute for Integrative Bioscience (Y.O.), National Institute for Basic Biology, National Institutes of Natural Sciences, The Graduate University for Advanced Studies (SOKENDAI), Okazaki, Aichi 444-8787, Japan; Department of Medical Cell Biology (S.H.), Institute of Molecular Embryology and Genetics, Kumamoto University, Chuo-ku, Kumamoto 860-0811, Japan; Division of Bioinformatics (T.S., M.S.), Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan; Institute of Biomedical Sciences (T.M.), University of Tokushima Graduate School, Tokushima 770-8503, Japan; Venetian Institute of Molecular Medicine (A.O.), 35129 Padua, Italy; and Department of Anti-Aging Medicine (S.I.), Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Matsumoto
authors.affiliation: Department of Developmental Genetics (S.M., K.S., G.Y.), Institute of Advanced Medicine, Wakayama Medical University, Wakayama 641-8509, Japan; Okazaki Institute for Integrative Bioscience (Y.O.), National Institute for Basic Biology, National Institutes of Natural Sciences, The Graduate University for Advanced Studies (SOKENDAI), Okazaki, Aichi 444-8787, Japan; Department of Medical Cell Biology (S.H.), Institute of Molecular Embryology and Genetics, Kumamoto University, Chuo-ku, Kumamoto 860-0811, Japan; Division of Bioinformatics (T.S., M.S.), Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan; Institute of Biomedical Sciences (T.M.), University of Tokushima Graduate School, Tokushima 770-8503, Japan; Venetian Institute of Molecular Medicine (A.O.), 35129 Padua, Italy; and Department of Anti-Aging Medicine (S.I.), Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Omori
authors.affiliation: Department of Developmental Genetics (S.M., K.S., G.Y.), Institute of Advanced Medicine, Wakayama Medical University, Wakayama 641-8509, Japan; Okazaki Institute for Integrative Bioscience (Y.O.), National Institute for Basic Biology, National Institutes of Natural Sciences, The Graduate University for Advanced Studies (SOKENDAI), Okazaki, Aichi 444-8787, Japan; Department of Medical Cell Biology (S.H.), Institute of Molecular Embryology and Genetics, Kumamoto University, Chuo-ku, Kumamoto 860-0811, Japan; Division of Bioinformatics (T.S., M.S.), Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan; Institute of Biomedical Sciences (T.M.), University of Tokushima Graduate School, Tokushima 770-8503, Japan; Venetian Institute of Molecular Medicine (A.O.), 35129 Padua, Italy; and Department of Anti-Aging Medicine (S.I.), Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Inoue
authors.affiliation: Department of Developmental Genetics (S.M., K.S., G.Y.), Institute of Advanced Medicine, Wakayama Medical University, Wakayama 641-8509, Japan; Okazaki Institute for Integrative Bioscience (Y.O.), National Institute for Basic Biology, National Institutes of Natural Sciences, The Graduate University for Advanced Studies (SOKENDAI), Okazaki, Aichi 444-8787, Japan; Department of Medical Cell Biology (S.H.), Institute of Molecular Embryology and Genetics, Kumamoto University, Chuo-ku, Kumamoto 860-0811, Japan; Division of Bioinformatics (T.S., M.S.), Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan; Institute of Biomedical Sciences (T.M.), University of Tokushima Graduate School, Tokushima 770-8503, Japan; Venetian Institute of Molecular Medicine (A.O.), 35129 Padua, Italy; and Department of Anti-Aging Medicine (S.I.), Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan.
authors.forename: Gen
authors.initials: G
authors.lastname: Yamada
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000728:Androgens / Q000378:metabolism*; D000818:Animals; D005260:Female; D018507:Gene Expression Regulation, Developmental; D051258:MafB Transcription Factor / Q000235:genetics*; D008297:Male; D008648:Mesoderm / Q000378:metabolism; D051379:Mice; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism; D020218:Response Elements / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D046468:Sexual Development / Q000235:genetics*; D059467:Transcriptome; D014521:Urethra / Q000196:embryology*
chemical_list: D020413:3' Untranslated Regions; D000728:Androgens; D051258:MafB Transcription Factor; C490406:Mafb protein, mouse; D011944:Receptors, Androgen