Kann, Martin, Ettou, Sandrine, Jung, Youngsook L., Lenz, Maximilian O., Taglienti, Mary E., Park, Peter J., Schermer, Bernhard ORCID: 0000-0002-5194-9000, Benzing, Thomas and Kreidberg, Jordan A. (2015). Genome-Wide Analysis of Wilms' Tumor 1-Controlled Gene Expression in Podocytes Reveals Key Regulatory Mechanisms. J. Am. Soc. Nephrol., 26 (9). S. 2097 - 2105. WASHINGTON: AMER SOC NEPHROLOGY. ISSN 1533-3450

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Abstract

The transcription factor Wilms' tumor suppressor 1 (WT1) is key to podocyte development and viability; however, WT1 transcriptional networks in podocytes remain elusive. We provide a comprehensive analysis of the genome-wide WT1 transcriptional network in podocytes in vivo using chromatin immunoprecipitation followed by sequencing (ChIPseq) and RNA sequencing techniques. Our data show a specific role for WT1 in regulating the podocyte-specific transcriptome through binding to both promoters and enhancers of target genes. Furthermore, we inferred a podocyte transcription factor network consisting of WT1, LMX1B, TCF21, Fox-class and TEAD family transcription factors, and MAFB that uses tissue-specific enhancers to control podocyte gene expression. In addition to previously described WT1-dependent target genes, ChIPseq identified novel WT1-dependent signaling systems. These targets included components of the Hippo signaling system, underscoring the power of genome-wide transcriptional-network analyses. Together, our data elucidate a comprehensive gene regulatory network in podocytes suggesting that WT1 gene regulatory function and podocyte cell-type specification can best be understood in the context of transcription factor-regulatory element network interplay.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Kann, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ettou, SandrineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jung, Youngsook L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lenz, Maximilian O.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Taglienti, Mary E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Park, Peter J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schermer, BernhardUNSPECIFIEDorcid.org/0000-0002-5194-9000UNSPECIFIED
Benzing, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kreidberg, Jordan A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-395658
DOI: 10.1681/ASN.2014090940
Journal or Publication Title: J. Am. Soc. Nephrol.
Volume: 26
Number: 9
Page Range: S. 2097 - 2105
Date: 2015
Publisher: AMER SOC NEPHROLOGY
Place of Publication: WASHINGTON
ISSN: 1533-3450
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
NEPHROTIC SYNDROME; WT1; LMX1B; DIFFERENTIATION; TRANSCRIPTION; SUPPRESSOR; FILTRATION; PROMOTER; YAP/TAZ; GROWTHMultiple languages
Urology & NephrologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/39565

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