Dong, Lihua and Pietsch, Stefan and Tan, Zenglai and Perner, Birgit and Sierig, Ralph and Kruspe, Dagmar and Groth, Marco and Witzgall, Ralph and Groene, Hermann-Josef and Platzer, Matthias and Englert, Christoph (2015) Integration of Cistromic and Transcriptomic Analyses Identifies Nphs2, Mafb, and Magi2 as Wilms' Tumor 1 Target Genes in Podocyte Differentiation and Maintenance. JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 26 (9). pp. 2118-2128. ISSN 1046-6673, 1533-3450
Full text not available from this repository. (Request a copy)Abstract
The Wilms' tumor suppressor gene 1 (WT1) encodes a zinc finger transcription factor. Mutation of WT1 in humans leads to Wilms' tumor, a pediatric kidney tumor, or other kidney diseases, such as Denys-Drash and Frasier syndromes. We showed previously that inactivation of WT1 in podocytes of adult mice results in proteinuria, foot process effacement, and glomerulosclerosis. However, the WT1-dependent transcriptional network regulating podocyte development and maintenance in vivo remains unknown. Here, we performed chromatin immunoprecipitation followed by high-throughput sequencing with glomeruli from wild-type mice. Additionally, we performed a cDNA microarray screen on an inducible podocyte-specific WT1 knockout mouse model. By integration of cistromic and transcriptomic analyses, we identified the WT1 targetome in mature podocytes. To further analyze the function and targets of WT1 in podocyte maturation, we used an Nphs2-Cre model, in which WT1 is deleted during podocyte differentiation. These mice display anuria and kidney hemorrhage and die within 24 hours after birth. To address the evolutionary conservation of WT1 targets, we performed functional assays using zebrafish as a model and identified Nphs2, Mafb, and Magi2 as novel WT1 target genes required for podocyte development. Our data also show that both Mafb and Magi2 are required for normal development of the embryonic zebrafish kidney. Collectively, our work provides insights into the transcriptional networks controlled by WT1 and identifies novel WT1 target genes that mediate the function of WT1 in podocyte differentiation and maintenance.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | GLOMERULAR-FILTRATION BARRIER; DENYS-DRASH SYNDROME; KIDNEY DEVELOPMENT; NEPHROTIC SYNDROME; SELF-ASSOCIATION; CELL BIOLOGY; WT1; PROTEIN; NEPHRIN; ZEBRAFISH; |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Anatomie > Lehrstuhl für Molekulare und zelluläre Anatomie > Prof. Dr. Ralph Witzgall |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 12 Jun 2019 13:47 |
| Last Modified: | 12 Jun 2019 13:47 |
| URI: | https://pred.uni-regensburg.de/id/eprint/4934 |
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