title: Research resource: transcriptome profiling of genes regulated by RXR and its permissive and nonpermissive partners in differentiating monocyte-derived dendritic cells.
abstract: 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical and Health Science Center, University of Debrecen, Egyetem Tér 1, H-4010 Debrecen, Hungary.
authors.forename: Lajos
authors.initials: L
authors.lastname: Széles
authors.forename: Szilárd
authors.initials: S
authors.lastname: Póliska
authors.forename: Gergely
authors.initials: G
authors.lastname: Nagy
authors.forename: Istvan
authors.initials: I
authors.lastname: Szatmari
authors.forename: Attila
authors.initials: A
authors.lastname: Szanto
authors.forename: Attila
authors.initials: A
authors.lastname: Pap
authors.forename: Malin
authors.initials: M
authors.lastname: Lindstedt
authors.forename: Saskia J A M
authors.initials: SJ
authors.lastname: Santegoets
authors.forename: Ralph
authors.initials: R
authors.lastname: Rühl
authors.forename: Balázs
authors.initials: B
authors.lastname: Dezsö
authors.forename: László
authors.initials: L
authors.lastname: Nagy
mesh_terms: D001565:Benzoates / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics*; D002460:Cell Line; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008024:Ligands; D000071518:Liver X Receptors; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D009539:Nicotinic Acids / Q000494:pharmacology; D057093:Orphan Nuclear Receptors / Q000819:agonists / Q000378:metabolism; D047494:PPAR delta / Q000819:agonists / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists / Q000378:metabolism; D010641:Phenotype; D018167:Receptors, Calcitriol / Q000819:agonists / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000819:agonists / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D001565:Benzoates; C493410:FABP4 protein, human; D050556:Fatty Acid-Binding Proteins; D008024:Ligands; D000071518:Liver X Receptors; D009539:Nicotinic Acids; D057093:Orphan Nuclear Receptors; D047494:PPAR delta; D047495:PPAR gamma; D018167:Receptors, Calcitriol; D018168:Receptors, Retinoic Acid; D013764:Tetrahydronaphthalenes; C068073:Am 580; D014212:Tretinoin; D013755:Tetradecanoylphorbol Acetate; C095104:LG 100268