title: Genome-wide binding and transcriptome analysis of human farnesoid X receptor in primary human hepatocytes.
abstract: OBJECTIVE
  Farnesoid X receptor (FXR, NR1H4) is a ligand-activated transcription factor, belonging to the nuclear receptor superfamily. FXR is highly expressed in the liver and is essential in regulating bile acid homeostasis. FXR deficiency is implicated in numerous liver diseases and mice with modulation of FXR have been used as animal models to study liver physiology and pathology. We have reported genome-wide binding of FXR in mice by chromatin immunoprecipitation - deep sequencing (ChIP-seq), with results indicating that FXR may be involved in regulating diverse pathways in liver. However, limited information exists for the functions of human FXR and the suitability of using murine models to study human FXR functions.
  
  
  METHODS
  In the current study, we performed ChIP-seq in primary human hepatocytes (PHHs) treated with a synthetic FXR agonist, GW4064 or DMSO control. In parallel, RNA deep sequencing (RNA-seq) and RNA microarray were performed for GW4064 or control treated PHHs and wild type mouse livers, respectively.
  
  
  RESULTS
  ChIP-seq showed similar profiles of genome-wide FXR binding in humans and mice in terms of motif analysis and pathway prediction. However, RNA-seq and microarray showed more different transcriptome profiles between PHHs and mouse livers upon GW4064 treatment.
  
  
  CONCLUSIONS
  In summary, we have established genome-wide human FXR binding and transcriptome profiles. These results will aid in determining the human FXR functions, as well as judging to what level the mouse models could be used to study human FXR functions.
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmacy, Rutgers University, Piscataway, New Jersey, United States of America; Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City, Kansas, United States of America.
authors.forename: Le
authors.initials: L
authors.lastname: Zhan
authors.affiliation: Department of Medical Pathology and Laboratory Medicine, University of California, Davis Health Systems, Sacramento, California, United States of America.
authors.forename: Hui-Xin
authors.initials: HX
authors.lastname: Liu
authors.affiliation: College of Science, Institute for Computer Applications, Huazhong Agricultural University, Wuhan, Hubei, China.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Fang
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmacy, Rutgers University, Piscataway, New Jersey, United States of America.
authors.forename: Bo
authors.initials: B
authors.lastname: Kong
authors.affiliation: Department of Medical Pathology and Laboratory Medicine, University of California, Davis Health Systems, Sacramento, California, United States of America.
authors.forename: Yuqi
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Connecticut, Storrs, Connecticut, United States of America.
authors.forename: Xiao-Bo
authors.initials: XB
authors.lastname: Zhong
authors.affiliation: Biometric Research Branch, National Cancer Institute, Rockville, Maryland, United States of America.
authors.forename: Jianwen
authors.initials: J
authors.lastname: Fang
authors.affiliation: Department of Medical Pathology and Laboratory Medicine, University of California, Davis Health Systems, Sacramento, California, United States of America.
authors.forename: Yu-Jui Yvonne
authors.initials: YJ
authors.lastname: Wan
authors.affiliation: Department of Pharmacology and Toxicology, School of Pharmacy, Rutgers University, Piscataway, New Jersey, United States of America; Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City, Kansas, United States of America.
authors.forename: Grace L
authors.initials: GL
authors.lastname: Guo
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation; D055106:Genome-Wide Association Study; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D008810:Mice, Inbred C57BL; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D059467:Transcriptome; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D018160:Receptors, Cytoplasmic and Nuclear; D000099150:Receptor, Farnesoid X-Activated