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  - 
TY  - JOUR
A1  - Herpin, Amaury
A1  - Schmidt, Cornelia
A1  - Kneitz, Susanne
A1  - Gobé, Clara
A1  - Regensburger, Martina
A1  - Le Cam, Aurélie
A1  - Montfort, Jérome
A1  - Adolfi, Mateus C.
A1  - Lillesaar, Christina
A1  - Wilhelm, Dagmar
A1  - Kraeussling, Michael
A1  - Mourot, Brigitte
A1  - Porcon, Béatrice
A1  - Pannetier, Maëlle
A1  - Pailhoux, Eric
A1  - Ettwiller, Laurence
A1  - Dolle, Dirk
A1  - Guiguen, Yann
A1  - Schartl, Manfred
T1  - A novel evolutionary conserved mechanism of RNA stability regulates synexpression of primordial germ cell-specific genes prior to the sex-determination stage in medaka
JF  - PLoS Biology
N2  - Dmrt1 is a highly conserved transcription factor, which is critically involved in regulation of gonad development of vertebrates. In medaka, a duplicate of dmrt1—acting as master sex-determining gene—has a tightly timely and spatially controlled gonadal expression pattern. In addition to transcriptional regulation, a sequence motif in the 3′ UTR (D3U-box) mediates transcript stability of dmrt1 mRNAs from medaka and other vertebrates. We show here that in medaka, two RNA-binding proteins with antagonizing properties target this D3U-box, promoting either RNA stabilization in germ cells or degradation in the soma. The D3U-box is also conserved in other germ-cell transcripts, making them responsive to the same RNA binding proteins. The evolutionary conservation of the D3U-box motif within dmrt1 genes of metazoans—together with preserved expression patterns of the targeting RNA binding proteins in subsets of germ cells—suggest that this new mechanism for controlling RNA stability is not restricted to fishes but might also apply to other vertebrates.
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-320011
VL  - 17
ER  -