Genome-wide binding and transcriptome analysis of human farnesoid X receptor in primary human hepatocytes

Le Zhan, Hui Xin Liu, Yaping Fang, Bo Kong, Yuqi He, Xiao Bo Zhong, Jianwen Fang, Yu-Jui Yvonne Wan, Grace L. Guo

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article numbere105930
JournalPLoS One
Volume9
Issue number9
DOIs
StatePublished - Sep 8 2014

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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    Zhan, L., Liu, H. X., Fang, Y., Kong, B., He, Y., Zhong, X. B., Fang, J., Wan, Y-J. Y., & Guo, G. L. (2014). Genome-wide binding and transcriptome analysis of human farnesoid X receptor in primary human hepatocytes. PLoS One, 9(9), [e105930]. https://doi.org/10.1371/journal.pone.0105930