Genome-wide interrogation of hepatic FXR reveals an asymmetric IR-1 motif and synergy with LRH-1

Title

Genome-wide interrogation of hepatic FXR reveals an asymmetric IR-1 motif and synergy with LRH-1

Creator

Chong H K; Infante A M; Seo Y K; Jeon T I; Zhang Y Q; Edwards P A; Xie X H; Osborne T F

Publisher

Nucleic Acids Research

Date

2010
2010-10

Description

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.

Subject

liver; orphan nuclear receptor; Biochemistry & Molecular Biology; binding; farnesoid X receptor; bile-acid; dna; activated receptor; fatty-acid synthase; ppar-gamma-rxr; target genes

Identifier

Format

Journal Article or Conference Abstract Publication

Search for Full-text

Users with a NEOMED Library login can search for full-text journal articles at the following url: https://libraryguides.neomed.edu/home

Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Pages

6007-6017

Issue

18

Volume

38

Citation

Chong H K; Infante A M; Seo Y K; Jeon T I; Zhang Y Q; Edwards P A; Xie X H; Osborne T F, “Genome-wide interrogation of hepatic FXR reveals an asymmetric IR-1 motif and synergy with LRH-1,” NEOMED Bibliography Database, accessed June 18, 2021, https://neomed.omeka.net/items/show/8934.

Social Bookmarking