title: Sox5 is involved in germ-cell regulation and sex determination in medaka following co-option of nested transposable elements creator: Schartl, Manfred creator: Schories, Susanne creator: Wakamatsu, Yuko creator: Nagao, Yusuke creator: Hashimoto, Hisashi creator: Bertin, ChloƩ creator: Mourot, Brigitte creator: Schmidt, Cornelia creator: Wilhelm, Dagmar creator: Centanin, Lazaro creator: Guiguen, Yann creator: Herpin, Amaury subject: ddc-570 subject: 570 Life sciences description: Background: Sex determination relies on a hierarchically structured network of genes, and is one of the most plastic processes in evolution. The evolution of sex-determining genes within a network, by neo- or sub-functionalization, also requires the regulatory landscape to be rewired to accommodate these novel gene functions. We previously showed that in medaka fish, the regulatory landscape of the master male-determining gene dmrt1bY underwent a profound rearrangement, concomitantly with acquiring a dominant position within the sex-determining network. This rewiring was brought about by the exaptation of a transposable element (TE) called Izanagi, which is co-opted to act as a silencer to turn off the dmrt1bY gene after it performed its function in sex determination. Results: We now show that a second TE, Rex1, has been incorporated into Izanagi. The insertion of Rex1 brought in a preformed regulatory element for the transcription factor Sox5, which here functions in establishing the temporal and cell-type-specific expression pattern of dmrt1bY. Mutant analysis demonstrates the importance of Sox5 in the gonadal development of medaka, and possibly in mice, in a dmrt1bY-independent manner. Moreover, Sox5 medaka mutants have complete female-to-male sex reversal. Conclusions: Our work reveals an unexpected complexity in TE-mediated transcriptional rewiring, with the exaptation of a second TE into a network already rewired by a TE. We also show a dual role for Sox5 during sex determination: first, as an evolutionarily conserved regulator of germ-cell number in medaka, and second, by de novo regulation of dmrt1 transcriptional activity during primary sex determination due to exaptation of the Rex1 transposable element. publisher: Springer ; BioMed Central date: 2018 type: Article type: info:eu-repo/semantics/article type: NonPeerReviewed format: application/pdf identifier: https://archiv.ub.uni-heidelberg.de/volltextserverhttps://archiv.ub.uni-heidelberg.de/volltextserver/24279/1/12915_2018_Article_485.pdf identifier: DOI:https://doi.org/10.1186/s12915-018-0485-8 identifier: urn:nbn:de:bsz:16-heidok-242799 identifier: Schartl, Manfred ; Schories, Susanne ; Wakamatsu, Yuko ; Nagao, Yusuke ; Hashimoto, Hisashi ; Bertin, ChloƩ ; Mourot, Brigitte ; Schmidt, Cornelia ; Wilhelm, Dagmar ; Centanin, Lazaro ; Guiguen, Yann ; Herpin, Amaury (2018) Sox5 is involved in germ-cell regulation and sex determination in medaka following co-option of nested transposable elements. BMC biology, 16 (16). pp. 1-17. ISSN 1747-7007 relation: https://archiv.ub.uni-heidelberg.de/volltextserver/24279/ rights: info:eu-repo/semantics/openAccess rights: Please see front page of the work (Sorry, Dublin Core plugin does not recognise license id) language: eng