FOXL2 transcriptionally represses Sf1 expression by antagonizing WT1 during ovarian development in mice

Takasawa, Kei, Kashimada, Kenichi, Pelosi, Emanuele, Takagi, Masatoshi, Morio, Tomohiro, Asahara, Hiroshi, Schlessinger, David, Mizutani, Shuki and Koopman, Peter (2014) FOXL2 transcriptionally represses Sf1 expression by antagonizing WT1 during ovarian development in mice. The FASEB Journal, Early Edition 5: 1-9. doi:10.1096/fj.13-246108

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Author Takasawa, Kei
Kashimada, Kenichi
Pelosi, Emanuele
Takagi, Masatoshi
Morio, Tomohiro
Asahara, Hiroshi
Schlessinger, David
Mizutani, Shuki
Koopman, Peter
Title FOXL2 transcriptionally represses Sf1 expression by antagonizing WT1 during ovarian development in mice
Formatted title
FOXL2 transcriptionally represses Sf1 expression by antagonizing WT1 during ovarian development in mice
Journal name The FASEB Journal   Check publisher's open access policy
ISSN 0892-6638
1530-6860
Publication date 2014-01-22
Sub-type Article (original research)
DOI 10.1096/fj.13-246108
Volume Early Edition
Issue 5
Start page 1
End page 9
Total pages 9
Place of publication Bethesda, MD, United States
Publisher Federation of American Societies for Experimental Biology
Collection year 2015
Language eng
Formatted abstract
Steroidogenic factor 1 (SF1; Ad4BP/NR5A1) plays key roles in gonadal development. Initially, the Sf1 gene is expressed in mouse fetal gonads of both sexes, but later is up-regulated in testes and down-regulated in ovaries. While Sf1 expression is activated and maintained by Wilms tumor 1 (WT1) and LIM homeobox 9 (LHX9), the mechanism of sex-specific regulation remains unclear. We hypothesized that Sf1 is repressed by the transcription factor Forkhead box L2 (FOXL2) during ovarian development. In an in vitro system (TM3 cells), up-regulation of Sf1 by the WT1 splice variant WT1-KTS was antagonized by FOXL2, as determined by quantitative RT-PCR. Using reporter assays, we localized the Sf1 proximal promoter region involved in this antagonism to a 674-bp interval. A conserved FOXL2 binding site was identified in this interval by in vitro chromatin immunoprecipitation. Introducing mutations into this site abolished negative regulation by FOXL2 in reporter assays. Finally, in Foxl2-null mice, Sf1 expression was increased 2-fold relative to wild-type XX fetal gonads. Our results support the hypothesis that FOXL2 negatively regulates Sf1 expression by antagonizing WT1-KTS during early ovarian development in mice.
Keyword Sex determination
Reproduction
LHX9
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
Institute for Molecular Bioscience - Publications
 
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Created: Tue, 25 Feb 2014, 23:40:21 EST by Susan Allen on behalf of Institute for Molecular Bioscience