Related Experiment Video
Updated: Apr 24, 2026
Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists
Published on: November 15, 2013
Genome-wide binding and transcriptome analysis of human farnesoid X receptor in primary human hepatocytes
Le Zhan1, Hui-Xin Liu2, Yaping Fang3
1Department 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.
Background & Aims:
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.
Insights
This study mapped human Farnesoid X receptor (FXR) binding sites and gene expression changes, finding similarities in binding but differences in transcriptome profiles compared to mice, informing the use of mouse models for human FXR research.
Area of Science:
- Hepatology and Molecular Biology
- Nuclear Receptor Signaling
Background:
- Farnesoid X receptor (FXR) is a nuclear receptor crucial for bile acid homeostasis and liver function.
- FXR dysfunction is linked to various liver diseases, making it a key target for therapeutic research.
- Current understanding of human FXR function and the utility of mouse models is limited.
Purpose of the Study:
- To establish genome-wide FXR binding profiles in primary human hepatocytes (PHHs).
- To characterize the human FXR-regulated transcriptome.
- To compare human FXR binding and transcriptional responses with those in mouse models.
Main Methods:
- Chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) in human hepatocytes treated with an FXR agonist.
- RNA sequencing (RNA-seq) and RNA microarray analysis of treated human hepatocytes and mouse livers.
- Comparative analysis of FXR binding and transcriptome data between humans and mice.
Main Results:
- Genome-wide FXR binding patterns showed similarities between humans and mice, including motif analysis and pathway predictions.
- Transcriptome profiles revealed significant differences between human hepatocytes and mouse livers following FXR activation.
- Established comprehensive human FXR binding and transcriptome datasets.
Conclusions:
- Human and mouse FXR binding sites are conserved, suggesting some functional overlap.
- Transcriptional responses to FXR activation differ between humans and mice, highlighting limitations of mouse models.
- The generated data provides a foundation for understanding human FXR functions and refining the use of animal models.
Related Concept Videos
01:31Transducer Mechanism: Nuclear Receptors
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
01:58Cell Specific Gene Expression
01:26Signal Transduction: Overview
Typically, signal transduction involves three...