Research Resource: Transcriptome Profiling of Genes Regulated by RXR and Its Permissive and Nonpermissive Partners in Differentiating Monocyte-Derived Dendritic Cells

Research Resource: Transcriptome Profiling of Genes Regulated by RXR and Its Permissive and Nonpermissive Partners in Differentiating Monocyte-Derived Dendritic Cells

Retinoid X receptors (RXRs) are heterodimerization partners for many nuclear receptors and also act as homodimers. Heterodimers formed by RXR and a nonpermissive partner, e.g. retinoic acid receptor (RAR) and vitamin D receptor (VDR), can be activated only by the agonist of the partner receptor. In...

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Main Authors: Széles, Lajos, Póliska, Szilárd, Nagy, Gergely, Szatmari, Istvan, Szanto, Attila, Pap, Attila, Lindstedt, Malin, Santegoets, Saskia J.A.M., Rühl, Ralph, Dezsö, Balázs, Nagy, László
Format: Online
Language:English
Published: The Endocrine Society 2010
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3051201/
id pubmed-3051201
recordtype oai_dc
spelling pubmed-30512012011-03-09 Research Resource: Transcriptome Profiling of Genes Regulated by RXR and Its Permissive and Nonpermissive Partners in Differentiating Monocyte-Derived Dendritic Cells Széles, Lajos Póliska, Szilárd Nagy, Gergely Szatmari, Istvan Szanto, Attila Pap, Attila Lindstedt, Malin Santegoets, Saskia J.A.M. Rühl, Ralph Dezsö, Balázs Nagy, László Research Resource Retinoid X receptors (RXRs) are heterodimerization partners for many nuclear receptors and also act as homodimers. Heterodimers formed by RXR and a nonpermissive partner, e.g. retinoic acid receptor (RAR) and vitamin D receptor (VDR), can be activated only by the agonist of the partner receptor. In contrast, heterodimers that contain permissive partners, e.g. liver X receptor (LXR) and peroxisome proliferator-activated receptor (PPAR), can be activated by agonists for either the partner receptor or RXR, raising the possibility of pleiotropic RXR signaling. However, it is not known to what extent the receptor’s activation results in triggering mechanisms dependent or independent of permissive heterodimers. In this study, we systematically and quantitatively characterized all probable RXR-signaling pathways in differentiating human monocyte-derived dendritic cells (Mo-DCs). Using pharmacological, microarray and quantitative RT-PCR techniques, we identified and characterized gene sets regulated by RXR agonists (LG100268 and 9-cis retinoic acid) and agonists for LXRs, PPARs, RARα, and VDR. Our results demonstrated that permissiveness was partially impaired in Mo-DCs, because a large number of genes regulated by PPAR or LXR agonists was not affected by RXR-specific agonists or was regulated to a lesser extent. As expected, we found that RXR agonists regulated only small portions of RARα or VDR targets. Importantly, we could identify and characterize PPAR- and LXR-independent pathways in Mo-DCs most likely mediated by RXR homodimers. These data suggested that RXR signaling in Mo-DCs was mediated via multiple permissive heterodimers and also by mechanism(s) independent of permissive heterodimers, and it was controlled in a cell-type and gene-specific manner. The Endocrine Society 2010-11 2010-09-22 /pmc/articles/PMC3051201/ /pubmed/20861222 http://dx.doi.org/10.1210/me.2010-0215 Text en Copyright © 2010 by The Endocrine Society This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/us/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Széles, Lajos
Póliska, Szilárd
Nagy, Gergely
Szatmari, Istvan
Szanto, Attila
Pap, Attila
Lindstedt, Malin
Santegoets, Saskia J.A.M.
Rühl, Ralph
Dezsö, Balázs
Nagy, László
spellingShingle Széles, Lajos
Póliska, Szilárd
Nagy, Gergely
Szatmari, Istvan
Szanto, Attila
Pap, Attila
Lindstedt, Malin
Santegoets, Saskia J.A.M.
Rühl, Ralph
Dezsö, Balázs
Nagy, László
Research Resource: Transcriptome Profiling of Genes Regulated by RXR and Its Permissive and Nonpermissive Partners in Differentiating Monocyte-Derived Dendritic Cells
author_facet Széles, Lajos
Póliska, Szilárd
Nagy, Gergely
Szatmari, Istvan
Szanto, Attila
Pap, Attila
Lindstedt, Malin
Santegoets, Saskia J.A.M.
Rühl, Ralph
Dezsö, Balázs
Nagy, László
author_sort Széles, Lajos
title Research Resource: Transcriptome Profiling of Genes Regulated by RXR and Its Permissive and Nonpermissive Partners in Differentiating Monocyte-Derived Dendritic Cells
title_short Research Resource: Transcriptome Profiling of Genes Regulated by RXR and Its Permissive and Nonpermissive Partners in Differentiating Monocyte-Derived Dendritic Cells
title_full Research Resource: Transcriptome Profiling of Genes Regulated by RXR and Its Permissive and Nonpermissive Partners in Differentiating Monocyte-Derived Dendritic Cells
title_fullStr Research Resource: Transcriptome Profiling of Genes Regulated by RXR and Its Permissive and Nonpermissive Partners in Differentiating Monocyte-Derived Dendritic Cells
title_full_unstemmed Research Resource: Transcriptome Profiling of Genes Regulated by RXR and Its Permissive and Nonpermissive Partners in Differentiating Monocyte-Derived Dendritic Cells
title_sort research resource: transcriptome profiling of genes regulated by rxr and its permissive and nonpermissive partners in differentiating monocyte-derived dendritic cells
description Retinoid X receptors (RXRs) are heterodimerization partners for many nuclear receptors and also act as homodimers. Heterodimers formed by RXR and a nonpermissive partner, e.g. retinoic acid receptor (RAR) and vitamin D receptor (VDR), can be activated only by the agonist of the partner receptor. In contrast, heterodimers that contain permissive partners, e.g. liver X receptor (LXR) and peroxisome proliferator-activated receptor (PPAR), can be activated by agonists for either the partner receptor or RXR, raising the possibility of pleiotropic RXR signaling. However, it is not known to what extent the receptor’s activation results in triggering mechanisms dependent or independent of permissive heterodimers. In this study, we systematically and quantitatively characterized all probable RXR-signaling pathways in differentiating human monocyte-derived dendritic cells (Mo-DCs). Using pharmacological, microarray and quantitative RT-PCR techniques, we identified and characterized gene sets regulated by RXR agonists (LG100268 and 9-cis retinoic acid) and agonists for LXRs, PPARs, RARα, and VDR. Our results demonstrated that permissiveness was partially impaired in Mo-DCs, because a large number of genes regulated by PPAR or LXR agonists was not affected by RXR-specific agonists or was regulated to a lesser extent. As expected, we found that RXR agonists regulated only small portions of RARα or VDR targets. Importantly, we could identify and characterize PPAR- and LXR-independent pathways in Mo-DCs most likely mediated by RXR homodimers. These data suggested that RXR signaling in Mo-DCs was mediated via multiple permissive heterodimers and also by mechanism(s) independent of permissive heterodimers, and it was controlled in a cell-type and gene-specific manner.
publisher The Endocrine Society
publishDate 2010
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3051201/
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