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Identification of hepatocyte nuclear factor‐1β gene regulatory networks in mouse kidney cells (690.9)
Author(s) -
Aboudehen Karam,
Patel Vishal,
Kim Min,
Xie Yang,
McDonald Jeffrey,
Gordillo Ruth,
Igarashi Peter
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.690.9
Subject(s) - biology , hepatocyte nuclear factors , hepatocyte nuclear factor 4 , transcription factor , chromatin immunoprecipitation , microarray analysis techniques , gene , microarray , sphingolipid , microbiology and biotechnology , gene expression , microrna , genetics , nuclear receptor , promoter
Hepatocyte nuclear factor‐1β (HNF‐1β) is a transcription factor that is expressed in renal tubules in the mammalian kidney. Mutations of HNF‐1β produce kidney cysts and electrolyte disorders. HNF‐1β has been shown to regulate the expression of cystic disease genes and solute transporters. The aim of this study was to identify the complete spectrum of genes that are regulated by HNF‐1β in the kidney. We performed genome‐wide chromatin immunoprecipitation and massively parallel sequencing (ChIP‐seq) in combination with microarray analysis to identify direct mRNA and miRNA targets in mouse mIMCD3 cells. ChIP‐seq analysis identified 4,725 mRNAs and 85 miRNAs as potential targets of HNF‐1β. Microarray analysis showed altered expression of 4,878 mRNAs and 51 miRNAs in cells expressing dominant‐negative mutant HNF‐1β. Combining the ChIP‐seq and microarray data identified 1,545 mRNAs and 22 miRNAs that were directly regulated by HNF‐1β. Pathway analysis revealed that HNF‐1β directly regulated the expression of multiple genes involved in cholesterol and sphingolipid metabolism. Liquid chromatography‐mass spectrometry showed corresponding alterations in the levels of sterols and sphingolipids in cells expressing mutant HNF‐1β. These findings provide new insights into the HNF‐1β transcriptional network in kidney cells and identify a novel role for HNF‐1β in regulating lipid metabolism in the kidney.