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

ABSTRACT: 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 ident

SUBMITTER: Chong HK 

PROVIDER: S-EPMC2952856 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature