دورية أكاديمية
Wilms tumor suppressor, WT1, suppresses epigenetic silencing of the β-catenin gene.
| العنوان: | Wilms tumor suppressor, WT1, suppresses epigenetic silencing of the β-catenin gene. |
|---|---|
| المؤلفون: | Akpa MM; From the Department of Human Genetics, McGill University, Montréal, Québec H3A 1B1 and., Iglesias DM; the Department of Paediatrics, Montreal Children's Hospital Research Institute, Montréal, Québec H3Z 2Z3, Canada., Chu LL; the Department of Paediatrics, Montreal Children's Hospital Research Institute, Montréal, Québec H3Z 2Z3, Canada., Cybulsky M; the Department of Paediatrics, Montreal Children's Hospital Research Institute, Montréal, Québec H3Z 2Z3, Canada., Bravi C; the Department of Paediatrics, Montreal Children's Hospital Research Institute, Montréal, Québec H3Z 2Z3, Canada., Goodyer PR; From the Department of Human Genetics, McGill University, Montréal, Québec H3A 1B1 and the Department of Paediatrics, Montreal Children's Hospital Research Institute, Montréal, Québec H3Z 2Z3, Canada paul.goodyer@mcgill.ca. |
| المصدر: | The Journal of biological chemistry [J Biol Chem] 2015 Jan 23; Vol. 290 (4), pp. 2279-88. Date of Electronic Publication: 2014 Oct 20. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Country of Publication: United States NLM ID: 2985121R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1083-351X (Electronic) Linking ISSN: 00219258 NLM ISO Abbreviation: J Biol Chem Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2021- : [New York, NY] : Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Original Publication: Baltimore, MD : American Society for Biochemistry and Molecular Biology |
| مواضيع طبية MeSH: | Epigenesis, Genetic*, Amnion/*metabolism , Histones/*metabolism , Polycomb Repressive Complex 2/*metabolism , WT1 Proteins/*metabolism , beta Catenin/*genetics, Amino Acid Motifs ; Cells, Cultured ; DNA Methylation ; Enhancer of Zeste Homolog 2 Protein ; Female ; Gene Expression Regulation, Developmental ; Gene Silencing ; Humans ; Mesenchymal Stem Cells/cytology ; Pregnancy ; Stem Cells/cytology ; Wilms Tumor/metabolism ; Wnt Proteins/metabolism ; beta Catenin/metabolism |
| مستخلص: | The mammalian kidney is derived from progenitor cells in intermediate mesoderm. During embryogenesis, progenitor cells expressing the Wilms tumor suppressor gene, WT1, are induced to differentiate in response to WNT signals from the ureteric bud. In hereditary Wilms tumors, clonal loss of WT1 precludes the β-catenin pathway response and leads to precancerous nephrogenic rests. We hypothesized that WT1 normally primes progenitor cells for differentiation by suppressing the enhancer of zeste2 gene (EZH2), involved in epigenetic silencing of differentiation genes. In human amniotic fluid-derived mesenchymal stem cells, we show that exogenous WT1B represses EZH2 transcription. This leads to a dramatic decrease in the repressive lysine 27 trimethylation mark on histone H3 that silences β-catenin gene expression. As a result, amniotic fluid mesenchymal stem cells acquire responsiveness to WNT9b and increase expression of genes that mark the onset of nephron differentiation. Our observations suggest that biallelic loss of WT1 sustains the inhibitory histone methylation state that characterizes Wilms tumors. (© 2015 by The American Society for Biochemistry and Molecular Biology, Inc.) |
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| معلومات مُعتمدة: | MOP-119571 Canada Canadian Institutes of Health Research |
| فهرسة مساهمة: | Keywords: Enhancer of Zeste Homolog 2 (EZH2); Epigenetic Silencing; Epigenetics; Kidney; Nephrogenesis; Polycomb; Polycomb Repressor Complex; Wilms Tumor Suppressor 1 (WT1); Wnt Pathway; β-Catenin (B-catenin) |
| المشرفين على المادة: | 0 (CTNNB1 protein, human) 0 (Histones) 0 (WT1 Proteins) 0 (WT1 protein, human) 0 (Wnt Proteins) 0 (beta Catenin) EC 2.1.1.43 (EZH2 protein, human) EC 2.1.1.43 (Enhancer of Zeste Homolog 2 Protein) EC 2.1.1.43 (Polycomb Repressive Complex 2) |
| تواريخ الأحداث: | Date Created: 20141022 Date Completed: 20150421 Latest Revision: 20211021 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC4303678 |
| DOI: | 10.1074/jbc.M114.573576 |
| PMID: | 25331950 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1083-351X |
|---|---|
| DOI: | 10.1074/jbc.M114.573576 |