scholarly journals The Schistosoma mansoni nuclear receptor FTZ-F1 maintains esophageal gland function via transcriptional regulation of meg-8.3

2021 ◽  
Vol 17 (12) ◽  
pp. e1010140
Author(s):  
Aracely A. Romero ◽  
Sarah A. Cobb ◽  
Julie N. R. Collins ◽  
Steven A. Kliewer ◽  
David J. Mangelsdorf ◽  
...  
Keyword(s):  
Nuclear Receptor ◽  
Chromatin Immunoprecipitation ◽  
Hormone Receptors ◽  
Transcriptional Profiling ◽  
Systematic Analysis ◽  
Esophageal Gland ◽  
Parasite Survival ◽  
Gland Function ◽  
Exon Gene ◽  
Transcriptional Target

Schistosomes infect over 200 million of the world’s poorest people, but unfortunately treatment relies on a single drug. Nuclear hormone receptors are ligand-activated transcription factors that regulate diverse processes in metazoans, yet few have been functionally characterized in schistosomes. During a systematic analysis of nuclear receptor function, we found that an FTZ-F1-like receptor was essential for parasite survival. Using a combination of transcriptional profiling and chromatin immunoprecipitation (ChIP), we discovered that the micro-exon gene meg-8.3 is a transcriptional target of SmFTZ-F1. We found that both Smftz-f1 and meg-8.3 are required for esophageal gland maintenance as well as integrity of the worm’s head. Together, these studies define a new role for micro-exon gene function in the parasite and suggest that factors associated with the esophageal gland could represent viable therapeutic targets.

Analysis of Chromatin–Nuclear Receptor Interactions by Laser-Chromatin Immunoprecipitation

2014 ◽  
pp. 25-34 ◽  
Author(s):  
Rosaria Benedetti ◽  
Mariarosaria Conte ◽  
Vincenzo Carafa ◽  
Bartolomeo Della Ventura ◽  
Carlo Altucci ◽  
...  
Keyword(s):  
Nuclear Receptor ◽  
Chromatin Immunoprecipitation ◽  
Receptor Interactions

scholarly journals Structure and Function of the Nuclear Receptor Superfamily and Current Targeted Therapies of Prostate Cancer

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1852 ◽  
Author(s):  
Baylee A. Porter ◽  
Maria A. Ortiz ◽  
Gennady Bratslavsky ◽  
Leszek Kotula
Keyword(s):  
Prostate Cancer ◽  
Transcription Factors ◽  
Nuclear Receptor ◽  
Hormone Receptors ◽  
Cell Permeability ◽  
Cancer Therapies ◽  
Functional Difference ◽  
Nuclear Receptor Superfamily ◽  
Functional Regulation ◽  
And Function

The nuclear receptor superfamily comprises a large group of proteins with functions essential for cell signaling, survival, and proliferation. There are multiple distinctions between nuclear superfamily classes defined by hallmark differences in function, ligand binding, tissue specificity, and DNA binding. In this review, we utilize the initial classification system, which defines subfamilies based on structure and functional difference. The defining feature of the nuclear receptor superfamily is that these proteins function as transcription factors. The loss of transcriptional regulation or gain of functioning of these receptors is a hallmark in numerous diseases. For example, in prostate cancer, the androgen receptor is a primary target for current prostate cancer therapies. Targeted cancer therapies for nuclear hormone receptors have been more feasible to develop than others due to the ligand availability and cell permeability of hormones. To better target these receptors, it is critical to understand their structural and functional regulation. Given that late-stage cancers often develop hormone insensitivity, we will explore the strengths and pitfalls of targeting other transcription factors outside of the nuclear receptor superfamily such as the signal transducer and activator of transcription (STAT).

scholarly journals Nuclear Hormone Receptors for Heme: REV-ERBα and REV-ERBβ Are Ligand-Regulated Components of the Mammalian Clock

2008 ◽  
Vol 22 (7) ◽  
pp. 1509-1520 ◽  
Author(s):  
Thomas P. Burris
Keyword(s):  
Nuclear Receptor ◽  
Cellular Differentiation ◽  
Target Gene ◽  
Hormone Receptors ◽  
Activation Function ◽  
Nuclear Hormone Receptors ◽  
Gene Promoters ◽  
Nuclear Receptor Corepressor ◽  
Small Molecule Ligands ◽  
Target Gene Transcription

Abstract The nuclear hormone receptors (NHRs), REV-ERBα and REV-ERBβ, regulate a number of physiological functions including the circadian rhythm, lipid metabolism, and cellular differentiation. These two receptors lack the activation function-2 region that is associated with the ability of NHRs to recruit coactivators and activate target gene transcription. These NHRs have been characterized as constitutive repressors of transcription due to their lack of an identified ligand and their strong ability to recruit the corepressor, nuclear receptor corepressor. Recently, the porphyrin heme was demonstrated to function as a ligand for both REV-ERBs. Heme binds directly to the ligand-binding domain and regulates the ability of these NHRs to recruit nuclear receptor corepressor to target gene promoters. This review focuses on the physiological roles that these two receptors play and the implications of heme functioning as their ligand. The prospect that these NHRs, now known to be regulated by small molecule ligands, may be targets for development of drugs for treatment of diseases associated with aberrant circadian rhythms including metabolic and psychiatric disorders as well as cancer is also addressed.

scholarly journals Minireview: Nuclear Receptor-Controlled Steroid Hormone Synthesis and Metabolism

2010 ◽  
Vol 24 (1) ◽  
pp. 11-21 ◽  
Author(s):  
Jinhan He ◽  
Qiuqiong Cheng ◽  
Wen Xie
Keyword(s):  
Transcription Factors ◽  
Dna Binding ◽  
Steroid Hormones ◽  
Nuclear Receptor ◽  
Recent Progress ◽  
Hormone Receptors ◽  
Steroid Hormone ◽  
Etiological Factor ◽  
Hormone Synthesis

Abstract Steroid hormones are essential in normal physiology whereas disruptions in hormonal homeostasis represent an important etiological factor for many human diseases. Steroid hormones exert most of their functions through the binding and activation of nuclear hormone receptors (NRs or NHRs), a superfamily of DNA-binding and often ligand-dependent transcription factors. In recent years, accumulating evidence has suggested that NRs can also regulate the biosynthesis and metabolism of steroid hormones. This review will focus on the recent progress in our understanding of the regulatory role of NRs in hormonal homeostasis and the implications of this regulation in physiology and diseases.

Nuclear receptor binding factor-1 (NRBF-1), a protein interacting with a wide spectrum of nuclear hormone receptors

Gene ◽  
1998 ◽  
Vol 221 (2) ◽  
pp. 225-233 ◽  
Author(s):  
Nobuyuki Masuda ◽  
Hiroaki Yasumo ◽  
Takashi Furusawa ◽  
Toshiro Tsukamoto ◽  
Hiroyuki Sadano ◽  
...  
Keyword(s):  
Nuclear Receptor ◽  
Receptor Binding ◽  
Hormone Receptors ◽  
Wide Spectrum ◽  
Nuclear Hormone Receptors ◽  
Binding Factor

Nuclear receptor binding factor-2 (NRBF-2), a possible gene activator protein interacting with nuclear hormone receptors

2000 ◽  
Vol 1490 (1-2) ◽  
pp. 189-197 ◽  
Author(s):  
Hiroaki Yasumo ◽  
Nobuyuki Masuda ◽  
Takashi Furusawa ◽  
Toshiro Tsukamoto ◽  
Hiroyuki Sadano ◽  
...  
Keyword(s):  
Nuclear Receptor ◽  
Receptor Binding ◽  
Hormone Receptors ◽  
Nuclear Hormone Receptors ◽  
Activator Protein ◽  
Binding Factor

scholarly journals A New Family of Nuclear Receptor Coregulators That Integrate Nuclear Receptor Signaling through CREB-Binding Protein

2000 ◽  
Vol 20 (14) ◽  
pp. 5048-5063 ◽  
Author(s):  
Muktar A. Mahajan ◽  
Herbert H. Samuels
Keyword(s):  
Nuclear Receptor ◽  
Hormone Receptors ◽  
Binding Protein ◽  
Nuclear Hormone Receptors ◽  
Dependent Manner ◽  
Creb Binding Protein ◽  
Activation Domain ◽  
High Affinity ◽  
New Family ◽  
Nuclear Receptor Coregulators

ABSTRACT We describe the cloning and characterization of a new family of nuclear receptor coregulators (NRCs) which modulate the function of nuclear hormone receptors in a ligand-dependent manner. NRCs are expressed as alternatively spliced isoforms which may exhibit different intrinsic activities and receptor specificities. The NRCs are organized into several modular structures and contain a single functional LXXLL motif which associates with members of the steroid hormone and thyroid hormone/retinoid receptor subfamilies with high affinity. Human NRC (hNRC) harbors a potent N-terminal activation domain (AD1), which is as active as the herpesvirus VP16 activation domain, and a second activation domain (AD2) which overlaps with the receptor-interacting LXXLL region. The C-terminal region of hNRC appears to function as an inhibitory domain which influences the overall transcriptional activity of the protein. Our results suggest that NRC binds to liganded receptors as a dimer and this association leads to a structural change in NRC resulting in activation. hNRC binds CREB-binding protein (CBP) with high affinity in vivo, suggesting that hNRC may be an important functional component of a CBP complex involved in mediating the transcriptional effects of nuclear hormone receptors.

scholarly journals Dax1 Up-Regulates Oct4 Expression in Mouse Embryonic Stem Cells via LRH-1 and SRA

2010 ◽  
Vol 24 (12) ◽  
pp. 2281-2291 ◽  
Author(s):  
Victoria R. Kelly ◽  
Bin Xu ◽  
Rork Kuick ◽  
Ronald J. Koenig ◽  
Gary D. Hammer
Keyword(s):  
Nuclear Receptor ◽  
Transcriptional Activation ◽  
Chromatin Immunoprecipitation ◽  
Target Genes ◽  
Embryonic Stem ◽  
Steroid Receptor ◽  
Orphan Nuclear Receptor ◽  
Steroidogenic Factor 1 ◽  
Oct4 Expression ◽  
Mes Cells

Abstract Dax1 (Nr0b1) is an atypical orphan nuclear receptor that has recently been shown to play a role in mouse embryonic stem (mES) cell pluripotency. Here we describe a mechanism by which Dax1 maintains pluripotency. In steroidogenic cells, Dax1 protein interacts with the NR5A nuclear receptor steroidogenic factor 1 (Nr5a1) to inhibit transcription of target genes. In mES cells, liver receptor homolog 1 (LRH-1, Nr5a2), the other NR5A family member, is expressed, and LRH-1 has been shown to interact with Dax1. We demonstrate by coimmunoprecipitation that Dax1 is, indeed, able to form a complex with LRH-1 in mES cells. Because Dax1 was historically characterized as an inhibitor of steroidogenic factor 1-mediated transcriptional activation, we hypothesized that Dax1 would inhibit LRH-1 action in mES cells. Therefore, we examined the effect of Dax1 on the LRH-1-mediated activation of the critical ES cell factor Oct4 (Pou5f1). Chromatin immunoprecipitation localized Dax1 to the Oct4 promoter at the LRH-1 binding site, and luciferase assays together with Dax1 overexpression and knockdown experiments revealed that, rather than repress, Dax1 accentuated LRH-1-mediated activation of the Oct4 gene. Similar to our previously published studies that defined the RNA coactivator steroid receptor RNA activator as the critical mediator of Dax1 coactivation function, Dax1 augmentation of LRH-1-mediated Oct4 activation is dependent upon steroid receptor RNA activator. Finally, utilizing published chromatin immunoprecipitation data of whole-genome binding sites of LRH-1 and Dax1, we show that LRH-1 and Dax1 commonly colocalize at 288 genes (43% of LRH-1 target genes), many of which are involved in mES cell pluripotency. Thus, our results indicate that Dax1 plays an important role in the maintenance of pluripotency in mES cells through interaction with LRH-1 and transcriptional activation of Oct4 and other genes.

scholarly journals Reduced Fat Mass in Mice Lacking Orphan Nuclear Receptor Estrogen-Related Receptor α

2003 ◽  
Vol 23 (22) ◽  
pp. 7947-7956 ◽  
Author(s):  
Jiangming Luo ◽  
Robert Sladek ◽  
Julie Carrier ◽  
Jo-Ann Bader ◽  
Denis Richard ◽  
...  
Keyword(s):  
Nuclear Receptor ◽  
Metabolic Regulation ◽  
Hormone Receptors ◽  
Target Genes ◽  
Serum Biochemistry ◽  
Orphan Nuclear Receptor ◽  
Steroid Synthesis ◽  
Fat Deposits ◽  
Estrogen Related Receptor

ABSTRACT The estrogen-related receptor α (ERRα) is an orphan member of the superfamily of nuclear hormone receptors expressed in tissues that preferentially metabolize fatty acids. Despite the molecular characterization of ERRα and identification of target genes, determination of its physiological function has been hampered by the lack of a natural ligand. To further understand the in vivo function of ERRα, we generated and analyzed Estrra-null (ERRα−/−) mutant mice. Here we show that ERRα−/− mice are viable, fertile and display no gross anatomical alterations, with the exception of reduced body weight and peripheral fat deposits. No significant changes in food consumption and energy expenditure or serum biochemistry parameters were observed in the mutant animals. However, the mutant animals are resistant to a high-fat diet-induced obesity. Importantly, DNA microarray analysis of gene expression in adipose tissue demonstrates altered regulation of several enzymes involved in lipid, eicosanoid, and steroid synthesis, suggesting that the loss of ERRα might interfere with other nuclear receptor signaling pathways. In addition, the microarray study shows alteration in the expression of genes regulating adipogenesis as well as energy metabolism. In agreement with these findings, metabolic studies showed reduced lipogenesis in adipose tissues. This study suggests that ERRα functions as a metabolic regulator and that the ERRα−/− mice provide a novel model for the investigation of metabolic regulation by nuclear receptors.

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