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http://purl.uniprot.org/citations/33453998http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/33453998http://www.w3.org/2000/01/rdf-schema#comment"Hepatocyte nuclear factor-1β (HNF-1β) is a tissue-specific transcription factor that is required for normal kidney development and renal epithelial differentiation. Mutations of HNF-1β produce congenital kidney abnormalities and inherited renal tubulopathies. Here, we show that ablation of HNF-1β in mIMCD3 renal epithelial cells results in activation of β-catenin and increased expression of lymphoid enhancer-binding factor 1 (LEF1), a downstream effector in the canonical Wnt signaling pathway. Increased expression and nuclear localization of LEF1 are also observed in cystic kidneys from Hnf1b mutant mice. Expression of dominant-negative mutant HNF-1β in mIMCD3 cells produces hyperresponsiveness to exogenous Wnt ligands, which is inhibited by siRNA-mediated knockdown of Lef1. WT HNF-1β binds to two evolutionarily conserved sites located 94 and 30 kb from the mouse Lef1 promoter. Ablation of HNF-1β decreases H3K27 trimethylation repressive marks and increases β-catenin occupancy at a site 4 kb upstream to Lef1. Mechanistically, WT HNF-1β recruits the polycomb-repressive complex 2 that catalyzes H3K27 trimethylation. Deletion of the β-catenin-binding domain of LEF1 in HNF-1β-deficient cells abolishes the increase in Lef1 transcription and decreases the expression of downstream Wnt target genes. The canonical Wnt target gene, Axin2, is also a direct transcriptional target of HNF-1β through binding to negative regulatory elements in the gene promoter. These findings demonstrate that HNF-1β regulates canonical Wnt target genes through long-range effects on histone methylation at Wnt enhancers and reveal a new mode of active transcriptional repression by HNF-1β."xsd:string
http://purl.uniprot.org/citations/33453998http://purl.org/dc/terms/identifier"doi:10.1074/jbc.ra120.015592"xsd:string
http://purl.uniprot.org/citations/33453998http://purl.uniprot.org/core/author"Patel V."xsd:string
http://purl.uniprot.org/citations/33453998http://purl.uniprot.org/core/author"Igarashi P."xsd:string
http://purl.uniprot.org/citations/33453998http://purl.uniprot.org/core/author"Chan S.C."xsd:string
http://purl.uniprot.org/citations/33453998http://purl.uniprot.org/core/author"Hajarnis S.S."xsd:string
http://purl.uniprot.org/citations/33453998http://purl.uniprot.org/core/author"Vrba S.M."xsd:string
http://purl.uniprot.org/citations/33453998http://purl.uniprot.org/core/date"2020"xsd:gYear
http://purl.uniprot.org/citations/33453998http://purl.uniprot.org/core/name"J Biol Chem"xsd:string
http://purl.uniprot.org/citations/33453998http://purl.uniprot.org/core/pages"17560-17572"xsd:string
http://purl.uniprot.org/citations/33453998http://purl.uniprot.org/core/title"Hepatocyte nuclear factor 1beta suppresses canonical Wnt signaling through transcriptional repression of lymphoid enhancer-binding factor 1."xsd:string
http://purl.uniprot.org/citations/33453998http://purl.uniprot.org/core/volume"295"xsd:string
http://purl.uniprot.org/citations/33453998http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/33453998
http://purl.uniprot.org/citations/33453998http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/33453998
http://purl.uniprot.org/uniprot/#_A0A0A0MQH4-mappedCitation-33453998http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/33453998
http://purl.uniprot.org/uniprot/#_D3Z654-mappedCitation-33453998http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/33453998
http://purl.uniprot.org/uniprot/#_F6XBL0-mappedCitation-33453998http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/33453998
http://purl.uniprot.org/uniprot/#_Q3TYB0-mappedCitation-33453998http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/33453998
http://purl.uniprot.org/uniprot/#_Q2M4H2-mappedCitation-33453998http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/33453998
http://purl.uniprot.org/uniprot/#_Q8BGZ9-mappedCitation-33453998http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/33453998
http://purl.uniprot.org/uniprot/#_P27782-mappedCitation-33453998http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/33453998
http://purl.uniprot.org/uniprot/#_P27889-mappedCitation-33453998http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/33453998
http://purl.uniprot.org/uniprot/#_Q3TEN5-mappedCitation-33453998http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/33453998
http://purl.uniprot.org/uniprot/#_Q8C402-mappedCitation-33453998http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/33453998