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Genome-Wide Binding and Transcriptome Analysis of Human Farnesoid X Receptor in Primary Human Hepatocytes

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 m...

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Autores principales: Zhan, Le, Liu, Hui-Xin, Fang, Yaping, Kong, Bo, He, Yuqi, Zhong, Xiao-bo, Fang, Jianwen, Wan, Yu-Jui Yvonne, Guo, Grace L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4157742/
https://www.ncbi.nlm.nih.gov/pubmed/25198545
http://dx.doi.org/10.1371/journal.pone.0105930
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author Zhan, Le
Liu, Hui-Xin
Fang, Yaping
Kong, Bo
He, Yuqi
Zhong, Xiao-bo
Fang, Jianwen
Wan, Yu-Jui Yvonne
Guo, Grace L.
author_facet Zhan, Le
Liu, Hui-Xin
Fang, Yaping
Kong, Bo
He, Yuqi
Zhong, Xiao-bo
Fang, Jianwen
Wan, Yu-Jui Yvonne
Guo, Grace L.
author_sort Zhan, Le
collection PubMed
description 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.
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spelling pubmed-41577422014-09-09 Genome-Wide Binding and Transcriptome Analysis of Human Farnesoid X Receptor in Primary Human Hepatocytes Zhan, Le Liu, Hui-Xin Fang, Yaping Kong, Bo He, Yuqi Zhong, Xiao-bo Fang, Jianwen Wan, Yu-Jui Yvonne Guo, Grace L. PLoS One Research Article 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. Public Library of Science 2014-09-08 /pmc/articles/PMC4157742/ /pubmed/25198545 http://dx.doi.org/10.1371/journal.pone.0105930 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
spellingShingle Research Article
Zhan, Le
Liu, Hui-Xin
Fang, Yaping
Kong, Bo
He, Yuqi
Zhong, Xiao-bo
Fang, Jianwen
Wan, Yu-Jui Yvonne
Guo, Grace L.
Genome-Wide Binding and Transcriptome Analysis of Human Farnesoid X Receptor in Primary Human Hepatocytes
title Genome-Wide Binding and Transcriptome Analysis of Human Farnesoid X Receptor in Primary Human Hepatocytes
title_full Genome-Wide Binding and Transcriptome Analysis of Human Farnesoid X Receptor in Primary Human Hepatocytes
title_fullStr Genome-Wide Binding and Transcriptome Analysis of Human Farnesoid X Receptor in Primary Human Hepatocytes
title_full_unstemmed Genome-Wide Binding and Transcriptome Analysis of Human Farnesoid X Receptor in Primary Human Hepatocytes
title_short Genome-Wide Binding and Transcriptome Analysis of Human Farnesoid X Receptor in Primary Human Hepatocytes
title_sort genome-wide binding and transcriptome analysis of human farnesoid x receptor in primary human hepatocytes
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4157742/
https://www.ncbi.nlm.nih.gov/pubmed/25198545
http://dx.doi.org/10.1371/journal.pone.0105930
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