Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 7900-7904 |
| Number of pages | 5 |
| Journal | Oncogene |
| Volume | 22 |
| Issue number | 39 |
| DOIs | |
| Publication status | Published - 2003 Sep 11 |
| Externally published | Yes |
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Keywords
- Gonad
- Sex determination
- Transcription factor
- Tumor-suppressor gene
ASJC Scopus subject areas
- Molecular Biology
- Cancer Research
- Genetics
Cite this
Transcriptional activity of testis-determining factor SRY is modulated by the Wilms' tumor 1 gene product, WT1. / Matsuzawa-Watanabe, Yumiko; Inoue, Jun Ichiro; Senba, Kentaro.
In: Oncogene, Vol. 22, No. 39, 11.09.2003, p. 7900-7904.Research output: Contribution to journal › Article
}
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 - Senba, Kentaro
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
UR - http://www.scopus.com/inward/record.url?scp=0345118133&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0345118133&partnerID=8YFLogxK
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 -