BioProject

Genome Wide mapping of Hnf-1β in kidney cells. Tissue-specific transcription factor that is expressed in the kidney and other epithelial organs. More...

Genome Wide mapping of Hnf-1β in kidney cells. Tissue-specific transcription factor that is expressed in the kidney and other epithelial organs. Humans with mutations in HNF1? develop kidney cysts, and HNF-1β regulates the transcription of several cystic disease genes. However, the complete spectrum of HNF-1β-regulated genes and pathways is not known. Here, we used ChIP-seq and DNA microarray analysis to identify 1,545 protein-coding genes that are directly regulated by HNF-1β in kidney epithelial cells. Pathway analysis predicted that HNF-1β regulates cholesterol metabolism. The expression of genes that are essential for cholesterol synthesis, including Srebf2 and Hmgcr, was reduced by expression of dominant-negative mutant HNF-1β or kidney-specific inactivation of HNF-1β. The levels of cholesterol biosynthetic intermediates and the rate of cholesterol synthesis were decreased in HNF-1β mutant cells. In addition, HNF-1β directly regulated the renal epithelial expression of PCSK9, a key regulator of cholesterol uptake, and depletion of cholesterol in the culture medium mitigated the inhibitory effects of mutant HNF-1β on SREBP-2 and HMGCR. These findings reveal a novel role of HNF-1β in regulating multiple steps in renal cholesterol metabolism. Overall design: Hnf-1β binding in 2 different samples. Immunoprecipitation of chromatin bound to HNF-1β in mIMCD3 cells was carried for two control (anti-IgG) and two experimental (anti-HNF-1β) samples. Less...