TY  - JOUR
A1  - Schartl, Manfred
A1  - Schories, Susanne
A1  - Watamatsu, Yuko
A1  - Nagao, Yusuke
A1  - Hashimoto, Hisashi
A1  - Bertin, Chloé
A1  - Mourot, Brigitte
A1  - Schmidt, Cornelia
A1  - Wilhelm, Dagmar
A1  - Centanin, Lazaro
A1  - Guiguen, Yann
A1  - Herpin, Amaury
T1  - Sox5 is involved in germ-cell regulation and sex determination in medaka following co-option of nested transposable elements
JF  - BMC Biology
N2  - 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.
KW  - Dmrt1bY
KW  - Sox5
KW  - exaptation
KW  - master sex-determining gene
KW  - transcriptional rewiring
KW  - medaka
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-175827
VL  - 16
IS  - 16
ER  -