TY - JOUR
T1 - Transcriptional activity of testis-determining factor SRY is modulated by the Wilms' tumor 1 gene product, WT1
AU - Matsuzawa-Watanabe, Yumiko
AU - Inoue, Jun Ichiro
AU - Semba, Kentaro
N1 - Funding Information:
We thank Drs M Yoshida, T Akiyama (Tokyo University), Y Kamachi, H Kondoh (Osaka University), K Nagai (Tokyo Medical University), N Takamatsu (Kitasato University), and K Morohashi (National Institute for Basic Biology) for providing materials and helpful discussions. We also thank Drs P Koopman (University of Queensland, Australia), A Menke (MRC, UK), and T Hunter (Salk Institute, USA) for critical reading of the manuscript. A Aono, N Hoshina, T Kimura, Y Wakabayashi, and M Yoshikawa provided excellent technical assistance. This work was supported by a grant provided by the Ichiro Kanehara Foundation (99KI005) and by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan.
PY - 2003/9/11
Y1 - 2003/9/11
N2 - The Wilms' tumor 1 (WT1) and sex-determining region of the Y chromosome (SRY) genes are essential for development of the mammalian gonads and mutations in these genes are associated with gonadal dysgenesis in humans. The SRY gene encodes a transcription factor with one high-mobility group (HMG) box as a DNA-binding domain. WT1 encodes a transcription factor that contains four contiguous C2H2-type zinc-finger motifs as a DNA/RNA binding or protein-protein interaction domain. Here we report that WT1 binds to and acts synergistically with SRY to activate transcription from a promoter containing SRY-binding sites. This interaction is mediated by the WT1 zinc-finger domain and the SRY HMG box. WT1 mutants associated with Denys-Drash syndrome (DDS), which is characterized by Wilms' tumor, pseudohermaphroditism, and nephropathy, fail to interact with SRY. Wildtype WT1 is recruited to SRY-binding sites in an SRY-dependent manner, whereas DDS mutants are not recruited as efficiently. These results suggest that WT1 forms a complex with SRY to regulate transcription and that this WT1-SRY interaction is important in testis development.
AB - The Wilms' tumor 1 (WT1) and sex-determining region of the Y chromosome (SRY) genes are essential for development of the mammalian gonads and mutations in these genes are associated with gonadal dysgenesis in humans. The SRY gene encodes a transcription factor with one high-mobility group (HMG) box as a DNA-binding domain. WT1 encodes a transcription factor that contains four contiguous C2H2-type zinc-finger motifs as a DNA/RNA binding or protein-protein interaction domain. Here we report that WT1 binds to and acts synergistically with SRY to activate transcription from a promoter containing SRY-binding sites. This interaction is mediated by the WT1 zinc-finger domain and the SRY HMG box. WT1 mutants associated with Denys-Drash syndrome (DDS), which is characterized by Wilms' tumor, pseudohermaphroditism, and nephropathy, fail to interact with SRY. Wildtype WT1 is recruited to SRY-binding sites in an SRY-dependent manner, whereas DDS mutants are not recruited as efficiently. These results suggest that WT1 forms a complex with SRY to regulate transcription and that this WT1-SRY interaction is important in testis development.
KW - Gonad
KW - Sex determination
KW - Transcription factor
KW - Tumor-suppressor gene
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U2 - 10.1038/sj.onc.1206717
DO - 10.1038/sj.onc.1206717
M3 - Article
C2 - 12970737
AN - SCOPUS:0345118133
VL - 22
SP - 7900
EP - 7904
JO - Oncogene
JF - Oncogene
SN - 0950-9232
IS - 39
ER -
