| http://purl.uniprot.org/citations/28577853 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/28577853 | http://www.w3.org/2000/01/rdf-schema#comment | "Hepatocyte nuclear factor 1 homeobox B (HNF1β) is an essential transcription factor for the development and functioning of the kidney. Mutations in HNF1β cause autosomal dominant tubulointerstitial kidney disease characterized by renal cysts and maturity-onset diabetes of the young (MODY). Moreover, these patients suffer from a severe electrolyte phenotype consisting of hypomagnesemia and hypokalemia. Until now, genes that are regulated by HNF1β are only partially known and do not fully explain the phenotype of the patients. Therefore, we performed chIP-seq in the immortalized mouse kidney cell line mpkDCT to identify HNF1β binding sites on a genome-wide scale. In total 7,421 HNF1β-binding sites were identified, including several genes involved in electrolyte transport and diabetes. A highly specific and conserved HNF1β site was identified in the promoter of Kcnj16 that encodes the potassium channel Kir5.1. Luciferase-promoter assays showed a 2.2-fold increase in Kcnj16 expression when HNF1β was present. Expression of the Hnf1β p.Lys156Glu mutant, previously identified in a patient with autosomal dominant tubulointerstitial kidney disease, did not activate Kcnj16 expression. Knockdown of Hnf1β in mpkDCT cells significantly reduced the appearance of Kcnj16 (Kir5.1) and Kcnj10 (Kir4.1) by 38% and 37%, respectively. These results were confirmed in a HNF1β renal knockout mouse which exhibited downregulation of Kcnj16, Kcnj10 and Slc12a3 transcripts in the kidney by 78%, 83% and 76%, respectively, compared to HNF1β wild-type mice. Thus, HNF1β is a transcriptional activator of Kcnj16. Hence, patients with HNF1β mutations may have reduced Kir5.1 activity in the kidney, resulting in hypokalemia and hypomagnesemia."xsd:string |
| http://purl.uniprot.org/citations/28577853 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.kint.2017.03.034"xsd:string |
| http://purl.uniprot.org/citations/28577853 | http://purl.uniprot.org/core/author | "Igarashi P."xsd:string |
| http://purl.uniprot.org/citations/28577853 | http://purl.uniprot.org/core/author | "Bindels R.J.M."xsd:string |
| http://purl.uniprot.org/citations/28577853 | http://purl.uniprot.org/core/author | "Hoenderop J.G.J."xsd:string |
| http://purl.uniprot.org/citations/28577853 | http://purl.uniprot.org/core/author | "de Baaij J.H.F."xsd:string |
| http://purl.uniprot.org/citations/28577853 | http://purl.uniprot.org/core/author | "Veenstra G.J.C."xsd:string |
| http://purl.uniprot.org/citations/28577853 | http://purl.uniprot.org/core/author | "Aboudehen K."xsd:string |
| http://purl.uniprot.org/citations/28577853 | http://purl.uniprot.org/core/author | "Kompatscher A."xsd:string |
| http://purl.uniprot.org/citations/28577853 | http://purl.uniprot.org/core/author | "Hoefnagels A.P.W.M."xsd:string |
| http://purl.uniprot.org/citations/28577853 | http://purl.uniprot.org/core/date | "2017"xsd:gYear |
| http://purl.uniprot.org/citations/28577853 | http://purl.uniprot.org/core/name | "Kidney Int"xsd:string |
| http://purl.uniprot.org/citations/28577853 | http://purl.uniprot.org/core/pages | "1145-1156"xsd:string |
| http://purl.uniprot.org/citations/28577853 | http://purl.uniprot.org/core/title | "Loss of transcriptional activation of the potassium channel Kir5.1 by HNF1beta drives autosomal dominant tubulointerstitial kidney disease."xsd:string |
| http://purl.uniprot.org/citations/28577853 | http://purl.uniprot.org/core/volume | "92"xsd:string |
| http://purl.uniprot.org/citations/28577853 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/28577853 |
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| http://purl.uniprot.org/uniprot/#_A2A5W8-mappedCitation-28577853 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/28577853 |
| http://purl.uniprot.org/uniprot/#_A8K434-mappedCitation-28577853 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/28577853 |
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| http://purl.uniprot.org/uniprot/#_Q8N538-mappedCitation-28577853 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/28577853 |