title: Coordinately Co-opted Multiple Transposable Elements Constitute an Enhancer for wnt5a Expression in the Mammalian Secondary Palate.
abstract: Acquisition of cis-regulatory elements is a major driving force of evolution, and there are several examples of developmental enhancers derived from transposable elements (TEs). However, it remains unclear whether one enhancer element could have been produced via cooperation among multiple, yet distinct, TEs during evolution. Here we show that an evolutionarily conserved genomic region named AS3_9 comprises three TEs (AmnSINE1, X6b_DNA and MER117), inserted side-by-side, and functions as a distal enhancer for wnt5a expression during morphogenesis of the mammalian secondary palate. Functional analysis of each TE revealed step-by-step retroposition/transposition and co-option together with acquisition of a binding site for Msx1 for its full enhancer function during mammalian evolution. The present study provides a new perspective suggesting that a huge variety of TEs, in combination, could have accelerated the diversity of cis-regulatory elements involved in morphological evolution.
authors.affiliation: Department of Life Science and Technology, Tokyo Institute of Technology, Midori-ku, Yokohama, Kanagawa, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Nishihara
authors.affiliation: Department of Life Science and Technology, Tokyo Institute of Technology, Midori-ku, Yokohama, Kanagawa, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Kobayashi
authors.affiliation: Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka Prefectural Hospital Organization, Izumi, Osaka, Japan.
authors.forename: Chiharu
authors.initials: C
authors.lastname: Kimura-Yoshida
authors.affiliation: Institute of Cell Biology and Neurobiology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Kuo
authors.initials: K
authors.lastname: Yan
authors.affiliation: Institute of Cell Biology and Neurobiology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Olga
authors.initials: O
authors.lastname: Bormuth
authors.affiliation: Department of Life Science and Technology, Tokyo Institute of Technology, Midori-ku, Yokohama, Kanagawa, Japan.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Ding
authors.affiliation: Department of Life Science and Technology, Tokyo Institute of Technology, Midori-ku, Yokohama, Kanagawa, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Nakanishi
authors.affiliation: Department of Life Science and Technology, Tokyo Institute of Technology, Midori-ku, Yokohama, Kanagawa, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sasaki
authors.affiliation: Bioinformatics Center, Institute for Chemical Research, Kyoto University, Gokasho, Uji, Kyoto, Japan.
authors.forename: Mika
authors.initials: M
authors.lastname: Hirakawa
authors.affiliation: National Institute of Genetics, Mishima, Shizuoka, Japan.
authors.forename: Kenta
authors.initials: K
authors.lastname: Sumiyama
authors.affiliation: Animal Resource Development Unit, RIKEN Center for Life Science Technologies, Chuou-ku, Kobe, Japan.|Genetic Engineering Team, RIKEN Center for Life Science Technologies, Chuou-ku, Kobe, Japan.
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Furuta
authors.affiliation: Institute of Cell Biology and Neurobiology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Victor
authors.initials: V
authors.lastname: Tarabykin
authors.affiliation: Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka Prefectural Hospital Organization, Izumi, Osaka, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Matsuo
authors.affiliation: Department of Life Science and Technology, Tokyo Institute of Technology, Midori-ku, Yokohama, Kanagawa, Japan.|Department of Life Sciences, National Cheng Kung University, Tainan, Taiwan.|Foundation for Advancement of International Science, Tsukuba, Japan.
authors.forename: Norihiro
authors.initials: N
authors.lastname: Okada
mesh_terms: D000818:Animals; D001665:Binding Sites; D004251:DNA Transposable Elements / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D019143:Evolution, Molecular; D005786:Gene Expression Regulation; D006801:Humans; D051957:MSX1 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D008322:Mammals; D051379:Mice; D018345:Mice, Knockout; D010159:Palate / Q000254:growth & development; D012045:Regulatory Sequences, Nucleic Acid; D019076:Transgenes; D000071818:Wnt-5a Protein / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D004251:DNA Transposable Elements; D004268:DNA-Binding Proteins; D051957:MSX1 Transcription Factor; C484084:Msx1 protein, mouse; D000071818:Wnt-5a Protein; C438615:Wnt5a protein, mouse