| WT1 transcription factor | OKDB#: 15 |
| Symbols: | WT1 | Species: | human | ||
| Synonyms: | GUD, AWT1, WAGR, WT33, NPHS4, WIT-2 | Locus: | 11p13 in Homo sapiens |
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| General Comment |
Wilms' tumor, or nephroblastoma, is associated with the WAGR syndrome that includes Wilms' tumor, congenital Aniridia, Genitourinary malformation, and mental Retardation. These abnormalities define a cluster of genes within chromosome 11p13 that are important in the development of the iris, kidney, urogenital tract (including the gonads), and brain. In addition, the Denys-Drash syndrome, the result of a dominant negative mutation of the WT1 gene, is characterized by glomerular nephropathy, bilateral Wilms' tumor and severe genitourinary malformation including streak gonads (Pelletier et al., 1991). However, more extensive analysis indicated that WT1 mutation only accounts for less than 10% of Wilms? tumors Coppes et al., 1993).(
NCBI Summary: This gene encodes a transcription factor that contains four zinc-finger motifs at the C-terminus and a proline/glutamine-rich DNA-binding domain at the N-terminus. It has an essential role in the normal development of the urogenital system, and it is mutated in a small subset of patients with Wilms tumor. This gene exhibits complex tissue-specific and polymorphic imprinting pattern, with biallelic, and monoallelic expression from the maternal and paternal alleles in different tissues. Multiple transcript variants have been described. In several variants, there is evidence for the use of a non-AUG (CUG) translation initiation codon upstream of, and in-frame with the first AUG. Authors of PMID:7926762 also provide evidence that WT1 mRNA undergoes RNA editing in human and rat, and that this process is tissue-restricted and developmentally regulated. [provided by RefSeq, Mar 2015] |
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| General function | Cell death/survival, Tumor suppressor, Nucleic acid binding, DNA binding, Transcription factor | ||||
| Comment | WT1 gene encodes a nuclear transcription factor with 4 Cys-His zinc fingers and a N-terminal region rich in Pro and Gln. The protein has sequence homology to the early growth response (EGR) gene family. | ||||
| Cellular localization | Nuclear | ||||
| Comment | Wilms' Tumor 1 Overexpression in Granulosa Cells Is Associated with Polycystic Ovaries in Polycystic Ovary Syndrome Patients. Wang Q et al. (2018) Polycystic ovary syndrome (PCOS) is a heterogeneous disorder characterized by chronic ovulatory dysfunction, hyperandrogenism, and polycystic ovaries. Wilms' tumor 1 (WT1) encoding a transcription factor involved in the differentiation of granulosa cells (GCs) regulates androgen receptor in the development of male genitalia. However, the expression pattern and possible role of WT1 in ovaries of PCOS patients are still unknown. GCs from 95 PCOS patients (PCOS group) and 62 healthy controls (control group) were isolated. The expression of WT1 in GCs was quantified using the reverse transcription-polymerase chain reaction. The correlation between WT1 expression and clinical characteristics was evaluated in PCOS patients. WT1 expression was increased in PCOS patients compared with the normal controls. The expression of WT1 was moderately correlated with testosterone (r = 0.334, p = 0.001) and luteinizing hormone (r = 0.357, p = 0.001) levels and the antral follicle counts (r = 0.337, p = 0.001). Our study provided novel insights into the relationship between hyperandrogenism and polycystic ovaries of PCOS and WT1.////////////////// Loss of WT1 expression in the endometrium of infertile PCOS patients: a hyperandrogenic effect? Gonzalez D et al. (2012) In fertile patients the endometrial Wilms tumor suppressor gene (WT1) is expressed during the window of implantation. Polycystic ovary syndrome (PCOS) patients suffer from hyperandrogenemia and infertility and have elevated endometrial androgen receptor (AR) expression. WT1 is known to be down-regulated by AR. Therefore, the expression of WT1 and its targets may be altered in PCOS endometrium. The objective of the study was to assess the expression and regulation of WT1 and selected downstream targets in secretory endometrium from ovulatory PCOS (ovPCOS) and fertile women. Endometrial samples were obtained from 25 ovPCOS and 25 fertile patients. Endometrial expression of WT1 and selected downstream targets were assessed by immunohistochemistry and RT-PCR. The androgen effect on WT1 expression was determined in vitro by immunoblots and RT-PCR. The expression of WT1 and its targets was quantified in fertile and ovPCOS stromal cells in the presence of androgens by RT-PCR. Caspase-3/7 activity was measured to evaluate sensitivity to drug-induced apoptosis. WT1 expression was down-regulated in secretory-phase ovPCOS endometrium. Stromal expression of Bcl-2 and p27 was higher, and epidermal growth factor receptor was lower in ovPCOS than in fertile patients. Endometrial stromal expression of WT1, Bcl-2, Bcl-2-associated X protein, and β-catenin was regulated by androgens. Apoptosis levels were reduced in ovPCOS samples and androgen-treated fertile samples. WT1 expression is down-regulated in ovPCOS endometrium during the window of implantation. Androgens regulate the expression of WT1 and its targets during endometrial decidualization. The altered balance between WT1 and AR in the endometrium of PCOS patients may jeopardize the success of decidualization and endometrial receptivity.////////////////// | ||||
| Ovarian function | Follicle development, Primary follicle growth, Preantral follicle growth | ||||
| Comment | Effects of WT1 Down-regulation on Oocyte Maturation and Preimplantation Embryo Development in Pigs. Gao F 2014 et al. The Wilms' tumor 1 gene (WT1), originally identified as a tumor suppressor associated with Wilms' tumors, encodes a zinc finger-containing transcription factor that is expressed in multiple tissues and is an important regulator of cellular and organ growth, proliferation, development, migration and survival. However, there is a deficiency of data regarding the expression and function of WT1 during oocyte maturation and preimplantation embryonic development. Here, we sought to define the expression characteristics and functions of WT1 during oocyte maturation and preimplantation embryonic development in pigs. We show that WT1 is expressed in porcine oocytes and at all preimplantation stages in embryos generated by intracytoplasmic sperm injection (ICSI). We then evaluated the effects of down-regulating WT1 expression at germinal vesicle (GV) and early ICSI stages using a recombinant plasmid (pGLV3-WT1-shRNA). Down-regulation of WT1 did not affect oocyte maturation but significantly decreased preimplantation embryo development and increased apoptosis in blastocysts. These results indicate that WT1 plays important roles in the development of porcine preimplantation embryos. ///////////////////////// Regulation of FSH receptor expression by the Wilms' tumor 1 gene product (WT1) in immature rat granulosa cells. Yoon O 2012 et al. ///////////////////////// Logan KA, et al reported the expression of wilms' tumor gene and protein localization during ovarian formation and follicular development in sheep. At Day 24 after conception, strong expression of WT1 mRNA and protein was observed in the coelomic epithelial region of the mesonephros where the gonad was forming. By Day 30, expression was observed in the surface epithelium and in many mesenchymal and endothelial cells of the gonad. Epithelial cells continued to express WT1 throughout gonadal development, as did pregranulosa cells during the process of follicular formation. However, WT1 expression was not observed in germ cells. During follicular growth, granulosa cells expressed WT1 from the type 1 (primordial) to the type 4 stages, but thereafter expression was reduced in type 5 (antral) follicles, consistent with the differentiation of granulosa cells into steroid-producing cells. The possible progenitor cells for the theca interna (i.e., the cell streams in the ovarian interstitium) expressed WT1 heterogeneously. However, differentiated theca cells in antral follicles did not express WT1. Strong expression of WT1 was observed during gonadal development, which is consistent with a role for WT1 in ovarian and follicular formation in the ewe. WT1 was identified in many cells of the neonatal and adult ovaries, including granulosa cells, suggesting that this factor is important for preantral follicular growth. However, the decline in WT1 expression in antral follicles suggests that WT1 may prevent premature differentiation of somatic cells of the follicle during early follicular growth. | ||||
| Expression regulated by | FSH, Growth Factors/ cytokines | ||||
| Comment | Treatment with estrogen or gonadotropins did not affect the concentration of ovarian WT1 mRNA (Hsu et al., 1995). Regulation of Wilms' tumor gene expression by nerve growth factor and follicle-stimulating hormone in the immature mouse ovary. Roh J et al. This study investigated the regulation of Wilms' tumor gene (WT1) in the ovary by nerve growth factor and FSH to better understand signals that initiate early follicular growth. Nerve growth factor showed a direct stimulatory effect on endogenous expression of WT1, whereas FSH attenuated basal and nerve growth factor-stimulated WT1 protein expression, which most likely depended on FSH responsiveness according to the follicle growth stage. | ||||
| Ovarian localization | Oocyte, Granulosa, Surface epithelium | ||||
| Comment | WT1 mRNA is expressed exclusively in the surface epithelium and granulosa cells of primordial, primary, and secondary rat follicles (Hsu et al., 1995). In situ hybridization analysis indicated the WT1 mRNAs are highly expressed in the kidney and in the genital ridge, fetal gonads and mesothelium of mice (Pritchard-Jones et al.,1991). | ||||
| Follicle stages | Primordial, Primary, Secondary | ||||
| Comment | Expressiom of WT1 mRNA is found in primordial, primary, and secondary rat follicles and it decreases during follicle growth (Hsu et al., 1995). In pig and monkey ovaries, WT1 expression was limited to granulosa cells of preantral follicles, as shown by in situ hybridization analysis. Thus, WT1 expression is restricted to immature follicles in diverse avian and mammalian species and over the reproductive life span in rats (Chun et al., 1999). | ||||
| Phenotypes |
POF (premature ovarian failure) |
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| Mutations |
4 mutations
Species: mouse
Species: mouse
Species: human
Species: human
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| Genomic Region | show genomic region | ||||
| Phenotypes and GWAS | show phenotypes and GWAS | ||||
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| created: | March 10, 1999, midnight | by: |
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| last update: | June 9, 2020, 1:10 p.m. | by: | hsueh email: |
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