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Text
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URL Address
<a href="http://doi.org/10.1093/nar/gkq397" target="_blank" rel="noreferrer noopener">http://doi.org/10.1093/nar/gkq397</a>
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Pages
6007-6017
Issue
18
Volume
38
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Title
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Genome-wide interrogation of hepatic FXR reveals an asymmetric IR-1 motif and synergy with LRH-1
Publisher
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Nucleic Acids Research
Date
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2010
2010-10
Subject
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liver; orphan nuclear receptor; Biochemistry & Molecular Biology; binding; farnesoid X receptor; bile-acid; dna; activated receptor; fatty-acid synthase; ppar-gamma-rxr; target genes
Creator
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Chong H K; Infante A M; Seo Y K; Jeon T I; Zhang Y Q; Edwards P A; Xie X H; Osborne T F
Description
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We used mouse hepatic chromatin enriched with an FXR antibody and chromatin immunoprecipitation-sequencing (ChIP-seq) to evaluate FXR binding on a genome-wide scale. This identified 1656 FXR-binding sites and 10% were located within 2 kb of a transcription start site which is much higher than predicted by random occurrence. A motif search uncovered a canonical nuclear receptor IR-1 site, consistent with in vitro DNA-binding studies reported previously. A separate nuclear receptor half-site for monomeric receptors such as LRH-1 was co-enriched and FXR activation of four newly identified promoters was significantly augmented by an LRH-1 expression vector in a co-transfection assay. There were 1038 genes located within 20 kb of a peak and a gene set enrichment analysis showed that genes identified by our ChIP-seq analysis are highly correlated with genes activated by an FXR-VP16 adenovirus in primary mouse hepatocytes providing functional relevance to the genome-wide binding study. Gene Ontology analysis showed FXR-binding sites close to many genes in lipid, fatty acid and steroid metabolism. Other broad gene clusters related to metabolism, transport, signaling and glycolysis were also significantly enriched. Thus, FXR may have a much wider role in cellular metabolism than previously appreciated.
Identifier
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<a href="http://doi.org/10.1093/nar/gkq397" target="_blank" rel="noreferrer noopener">10.1093/nar/gkq397</a>
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Journal Article or Conference Abstract Publication
2010
activated receptor
bile-acid
Binding
Biochemistry & Molecular Biology
Chong H K
DNA
Edwards P A
Farnesoid X receptor
fatty-acid synthase
Infante A M
Jeon T I
Journal Article or Conference Abstract Publication
Liver
Nucleic acids research
orphan nuclear receptor
Osborne T F
ppar-gamma-rxr
Seo Y K
target genes
Xie X H
Zhang Y Q