Cloning of a cDNA encoding the murine orphan receptor RZR/RORγ and characterization of its response element

Medvedev, Alexander V.; Yan, Zhonghua; Hirose, Takahisa; Giguère, Vincent; Jetten, Anton M.

doi:10.1016/s0378-1119(96)00504-5

Cited by 114 publications

(110 citation statements)

References 22 publications

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“…The Rorc gene encodes two isoforms, RORγ and RORγt, with distinct transcriptional start sites. RORγ-specific exons 1 and 2 and RORγt-specific exon 1 are spliced to the common exons 3 to 11, resulting in two proteins that differ only at their N-terminal ends [15][16][17][18]. Unlike RORγ, which is expressed in many tissues such as brain, heart, kidney, liver, lung, and muscle, RORγt has been detected exclusively in cells of the lymphoid lineage [19].…”

Section: Rorγt: a Master Regulator Of The Th17 Cell Lineage?mentioning

confidence: 99%

Transcriptional regulation of Th17 cell differentiation

Ivanov¹,

Zhou²,

Littman³

2007

Seminars in Immunology

423

321

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The paradigm of effector T helper cell differentiation into either Th1 or Th2 lineages has been profoundly shaken by the discovery of T cells that secrete IL-17 and other inflammatory cytokines. This subset, referred to as Th17, is centrally involved in autoimmune disease and is important in host defense at mucosal surfaces. In mouse, a series of cytokines, including IL-6, IL-21, IL-23, and TGF-β, function sequentially or synergistically to induce the Th17 lineage. Other cytokines, including IL-2, IL-4, IFNγ, and IL-27, inhibit differentiation of this lineage. Here we review how the nuclear orphan receptor RORγt functions to coordinate the diverse cytokine-induced signals and thus control Th17 cell differentiation.

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Section: Rorγt: a Master Regulator Of The Th17 Cell Lineage?mentioning

confidence: 99%

Transcriptional regulation of Th17 cell differentiation

Ivanov¹,

Zhou²,

Littman³

2007

Seminars in Immunology

423

321

View full text Add to dashboard Cite

show abstract

“…Proteins of the ROR family display a typical nuclear receptor domain structure consisting of four domains: an N-terminal domain, a highly conserved DNA-binding domain (DBD), a hinge domain, and a C-terminal ligand-binding domain. The DBD binds to DNA, containing a so-called ROR response element (RORE), which consists of the DNA sequence GGTCA as a core motive, preceded by an A/T-rich sequence (28,29). In contrast to other nuclear receptors, ROR family proteins bind DNA as monomers (26,28,30).…”

Section: D4mentioning

confidence: 99%

“…The DBD binds to DNA, containing a so-called ROR response element (RORE), which consists of the DNA sequence GGTCA as a core motive, preceded by an A/T-rich sequence (28,29). In contrast to other nuclear receptors, ROR family proteins bind DNA as monomers (26,28,30). They can interact with both coactivators and corepressors to positively or negatively regulate transcription of target genes and are involved in a wide range of differentiation processes.…”

Section: D4mentioning

confidence: 99%

RORC2 Is Involved in T Cell Polarization through Interaction with the FOXP3 Promoter

Bürgler¹,

Mantel

Bassin³

et al. 2010

The Journal of Immunology

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“…It is now well recognized that obesity is associated with chronic low-grade inflammation and that inflammatory processes play an important role in obesity and related pathologies (18,44,53). Infiltration of macrophages and various T-lymphocytes in hypertrophic adipose tissues have been considered as important early events in the development of obesity-associated complications (14, 38, 57) and the release of proinflammatory cytokines by adipose tissue plays a key role in the development of insulin resistance, NAFDL, and cardiovascular disease.Retinoid-related orphan receptors ROR␣, ␤, and ␥ (NR1F1-3) constitute a subfamily of nuclear receptors that regulate gene transcription by binding as a monomer to ROR-response elements (RORE) in the regulatory region of target genes (15,20,35). Recent studies have demonstrated that RORs function as ligand-dependent transcription factors (20,23,30,48,55).…”

mentioning

confidence: 99%

“…Retinoid-related orphan receptors ROR␣, ␤, and ␥ (NR1F1-3) constitute a subfamily of nuclear receptors that regulate gene transcription by binding as a monomer to ROR-response elements (RORE) in the regulatory region of target genes (15,20,35). Recent studies have demonstrated that RORs function as ligand-dependent transcription factors (20,23,30,48,55).…”

mentioning

confidence: 99%

Transcriptional profiling reveals a role for RORα in regulating gene expression in obesity-associated inflammation and hepatic steatosis

Kang¹,

Okamoto²,

Takeda³

et al. 2011

Physiological Genomics

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AM. Transcriptional profiling reveals a role for ROR␣ in regulating gene expression in obesity-associated inflammation and hepatic steatosis. Physiol Genomics 43: 818 -828, 2011. First published May 3, 2011 doi:10.1152/physiolgenomics.00206.2010.-Retinoid-related orphan receptor (ROR)␣4 is the major ROR␣ isoform expressed in adipose tissues and liver. In this study we demonstrate that ROR␣-deficient staggerer mice (ROR␣ sg/sg ) fed with a high-fat diet (HFD) exhibited reduced adiposity and hepatic triglyceride levels compared with wild-type (WT) littermates and were resistant to the development of hepatic steatosis, adipose-associated inflammation, and insulin resistance. Gene expression profiling showed that many genes involved in triglyceride synthesis and storage, including Cidec, Cidea, and Mogat1, were expressed at much lower levels in liver of ROR␣ sg/sg mice. In contrast, overexpression of ROR␣ in mouse hepatoma Hepa1-6 cells significantly increased the expression of genes that were repressed in ROR␣ sg/sg liver, including Sult1b1, Adfp, Cidea, and ApoA4. ChIP and promoter analysis suggested that several of these genes were regulated directly by ROR␣. In addition to reduced lipid accumulation, inflammation was greatly diminished in white adipose tissue (WAT) of ROR␣ sg/sg mice fed with an HFD. The infiltration of macrophages and the expression of many immune response and proinflammatory genes, including those encoding various chemo/cytokines, Toll-like receptors, and TNF signaling proteins, were significantly reduced in ROR␣ sg/sg WAT. Moreover, ROR␣ sg/sg mice fed with an HFD were protected from the development of insulin resistance. ROR␣ sg/sg mice consumed more oxygen and produced more carbon dioxide, suggesting increased energy expenditure in this genotype. Our study indicates that ROR␣ plays a critical role in the regulation of several aspects of metabolic syndrome. Therefore, ROR␣ may provide a novel therapeutic target in the management of obesity and associated metabolic diseases. staggerer mice; obesity; metabolic syndrome; macrophage; insulinresistance; diabetes; retinoid-related orphan receptors OBESITY IS A MAJOR GLOBAL health concern. In the United States alone, 30% of the general population is obese and an estimated 66% of all adults are overweight (40). Obesity is associated with an elevated risk of several pathologies, including Type 2 diabetes, cardiovascular disease, nonalcoholic fatty liver disease (NAFLD), cancer, and airway disease (18,36). The molecular links between obesity and these diseases are beginning to be understood. It is now well recognized that obesity is associated with chronic low-grade inflammation and that inflammatory processes play an important role in obesity and related pathologies (18,44,53). Infiltration of macrophages and various T-lymphocytes in hypertrophic adipose tissues have been considered as important early events in the development of obesity-associated complications (14, 38, 57) and the release of proinflammatory cytokines by adipose tissue plays a key ...

show abstract

Cloning of a cDNA encoding the murine orphan receptor RZR/RORγ and characterization of its response element

Cited by 114 publications

References 22 publications

Transcriptional regulation of Th17 cell differentiation

Transcriptional regulation of Th17 cell differentiation

RORC2 Is Involved in T Cell Polarization through Interaction with the FOXP3 Promoter

Transcriptional profiling reveals a role for RORα in regulating gene expression in obesity-associated inflammation and hepatic steatosis

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