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https://www.readbyqxmd.com/read/28317936/priming-of-transcriptional-memory-responses-via-the-chromatin-accessibility-landscape-in-t-cells
#1
Wen Juan Tu, Kristine Hardy, Christopher R Sutton, Robert McCuaig, Jasmine Li, Jenny Dunn, Abel Tan, Vedran Brezar, Melanie Morris, Gareth Denyer, Sau Kuen Lee, Stephen J Turner, Nabila Seddiki, Corey Smith, Rajiv Khanna, Sudha Rao
Memory T cells exhibit transcriptional memory and "remember" their previous pathogenic encounter to increase transcription on re-infection. However, how this transcriptional priming response is regulated is unknown. Here we performed global FAIRE-seq profiling of chromatin accessibility in a human T cell transcriptional memory model. Primary activation induced persistent accessibility changes, and secondary activation induced secondary-specific opening of previously less accessible regions associated with enhanced expression of memory-responsive genes...
March 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28283662/exhaustion-associated-regulatory-regions-in-cd8-tumor-infiltrating-t-cells
#2
Giuliana P Mognol, Roberto Spreafico, Victor Wong, James P Scott-Browne, Susan Togher, Alexander Hoffmann, Patrick G Hogan, Anjana Rao, Sara Trifari
T-cell exhaustion is a progressive loss of effector function and memory potential due to persistent antigen exposure, which occurs in chronic viral infections and cancer. Here we investigate the relation between gene expression and chromatin accessibility in CD8(+) tumor-infiltrating lymphocytes (TILs) that recognize a model tumor antigen and have features of both activation and functional exhaustion. By filtering out accessible regions observed in bystander, nonexhausted TILs and in acutely restimulated CD8(+) T cells, we define a pattern of chromatin accessibility specific for T-cell exhaustion, characterized by enrichment for consensus binding motifs for Nr4a and NFAT transcription factors...
March 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28249906/nr4a3-suppresses-lymphomagenesis-through-induction-of-pro-apoptotic-genes
#3
Alexander Ja Deutsch, Beate Rinner, Martin Pichler, Katharina Troppan, Katrin Pansy, Marco Bischof, Karoline Fechter, Stefan Hatzl, Julia Feichtinger, Kerstin Wenzl, Marie-Therese Frisch, Verena Stiegelbauer, Andreas Prokesch, Anne Margrethe Krogsdam, Heinz Sill, Gerhard G Thallinger, Hildegard T Greinix, Chenguang Wang, Christine Beham-Schmid, Peter Neumeister
Nuclear orphan receptor NR4A1 exerts an essential tumor suppressor function in aggressive lymphomas. In this study, we investigated the hypothesized contribution of the related NR4A family member NR4A3 to lymphomagenesis. In aggressive lymphoma patients, low expression of NR4A3 was associated with poor survival. Ectopic expression or pharmacological activation of NR4A3 in lymphoma cell lines led to a significantly higher proportion of apoptotic cells. In a mouse NSG xenograft model of lymphoma (stably transduced SuDHL4 cells), NR4A3 expression abrogated tumor growth, compared to vector control and uninduced cells which formed massive tumors...
March 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28198082/pck1-expression-is-correlated-with-the-plasma-glucose-level-in-the-duck
#4
L Chen, T Zeng, G Q Li, R Liu, Y Tian, Q H Li, L Z Lu
Phosphoenolpyruvate carboxykinase 1 (soluble) (PCK1) is a key gene in gluconeogenesis and glyceroneogenesis. Although its functions have been extensively studied in mice, bats and humans, little is known in ducks. Here, PCK1 functions were studied using a duck domestication model and a 48-h fasting experiment. We found PCK1 expression significantly decreased in two breeds of domestic ducks (Jinyun Pockmark ducks and Cherry Valley ducks) as compared with wild ducks (Anas platyrhynchos). Simultaneously, plasma levels of glucose, triglycerides and free fatty acid in domestic ducks were lower than in wild ducks...
February 15, 2017: Animal Genetics
https://www.readbyqxmd.com/read/28167941/nr4a-receptors-differentially-regulate-nf-%C3%AE%C2%BAb-signaling-in-myeloid-cells
#5
Caitriona McEvoy, Monica de Gaetano, Hugh E Giffney, Bojlul Bahar, Eoin P Cummins, Eoin P Brennan, Mary Barry, Orina Belton, Catherine G Godson, Evelyn P Murphy, Daniel Crean
Dysregulation of inflammatory responses is a hallmark of multiple diseases such as atherosclerosis and rheumatoid arthritis. As constitutively active transcription factors, NR4A nuclear receptors function to control the magnitude of inflammatory responses and in chronic inflammatory disease can be protective or pathogenic. Within this study, we demonstrate that TLR4 stimulation using the endotoxin lipopolysaccharide (LPS) rapidly enhances NR4A1-3 expression in human and murine, primary and immortalized myeloid cells with concomitant gene transcription and protein secretion of MIP-3α, a central chemokine implicated in numerous pathologies...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28055275/the-nr4a-subfamily-of-nuclear-receptors-potential-new-therapeutic-targets-for-the-treatment-of-inflammatory-diseases
#6
Ricardo Rodríguez-Calvo, Marta Tajes, Manuel Vázquez-Carrera
Prolonged inflammatory response contributes to the pathogenesis of chronic disease-related disturbances. Among nuclear receptors (NRs), the orphan NR4A subfamily, which includes Nur77 (NR4A1), Nurr1 (NR4A2) and NOR1 (NR4A3), has recently emerged as a therapeutic target for the treatment of inflammation. Areas covered: This review focuses on the capacity of NR4A receptors to counter-regulate the development of the inflammatory response, with a special focus on the molecular transrepression mechanisms. Expert opinion: Recent studies have highlighted the role of NR4A receptors as significant regulators of the inflammatory response...
January 12, 2017: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/27992436/transcriptomic-analysis-shows-decreased-cortical-expression-of-nr4a1-nr4a2-and-rxrb-in-schizophrenia-and-provides-evidence-for-nuclear-receptor-dysregulation
#7
Susan M Corley, Shan-Yuan Tsai, Marc R Wilkins, Cynthia Shannon Weickert
Many genes are differentially expressed in the cortex of people with schizophrenia, implicating factors that control transcription more generally. Hormone nuclear receptors dimerize to coordinate context-dependent changes in gene expression. We hypothesized that members of two families of nuclear receptors (NR4As), and retinoid receptors (RARs and RXRs), are altered in the dorsal lateral prefrontal cortex (DLPFC) of people with schizophrenia. We used next generation sequencing and then qPCR analysis to test for changes in mRNA levels for transcripts encoding nuclear receptors: orphan nuclear receptors (3 in the NR4A, 3 in the RAR, 3 in the RXR families and KLF4) in total RNA extracted from the DLPFC from people with schizophrenia compared to controls (n = 74)...
2016: PloS One
https://www.readbyqxmd.com/read/27939672/dynamic-changes-in-chromatin-accessibility-occur-in-cd8-t-cells-responding-to-viral-infection
#8
James P Scott-Browne, Isaac F López-Moyado, Sara Trifari, Victor Wong, Lukas Chavez, Anjana Rao, Renata M Pereira
In response to acute infection, naive CD8(+) T cells expand, differentiate into effector cells, and then contract to a long-lived pool of memory cells after pathogen clearance. During chronic infections or in tumors, CD8(+) T cells acquire an "exhausted" phenotype. Here we present genome-wide comparisons of chromatin accessibility and gene expression from endogenous CD8(+) T cells responding to acute and chronic viral infection using ATAC-seq and RNA-seq techniques. Acquisition of effector, memory, or exhausted phenotypes was associated with stable changes in chromatin accessibility away from the naive T cell state...
December 20, 2016: Immunity
https://www.readbyqxmd.com/read/27913963/erratum-to-altered-nr4a-subfamily-gene-expression-level-in-peripheral-blood-of-parkinson-s-and-alzheimer-s-disease-patients
#9
Francesca Montarolo, Simona Perga, Serena Martire, De'sire'e Nicole Navone, Alberto Marchet, Daniela Leotta, Antonio Bertolotto
No abstract text is available yet for this article.
December 2, 2016: Neurotoxicity Research
https://www.readbyqxmd.com/read/27871853/nur77-downregulation-triggers-pulmonary-artery-smooth-muscle-cell-proliferation-and-migration-in-mice-with-hypoxic-pulmonary-hypertension-via-the-axin2-%C3%AE-catenin-signaling-pathway
#10
Xiaowei Nie, Jianxin Tan, Youai Dai, Wenjun Mao, Yuan Chen, Guowei Qin, Guirong Li, Chenyou Shen, Jingjing Zhao, Jingyu Chen
Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by remodeling of the pulmonary vasculature, including marked proliferation and reduced apoptosis of pulmonary artery smooth muscle cells (PASMCs). Members of the nuclear receptor 4A (NR4A) subfamily are involved in a variety of biological events, such as cell apoptosis, proliferation, inflammation, and metabolism. Activation of Nur77 (an orphan nuclear receptor that belongs to NR4A subfamily) has recently been reported to be as a beneficial agent in the treatment of cardiovascular and metabolic diseases...
December 2016: Vascular Pharmacology
https://www.readbyqxmd.com/read/27834392/pharmacological-activators-of-the-nr4a-nuclear-receptors-enhance-ltp-in-a-creb-cbp-dependent-manner
#11
Morgan S Bridi, Joshua D Hawk, Snehajyoti Chatterjee, Stephen Safe, Ted Abel
Nr4a nuclear receptors contribute to long-term memory formation and are required for long-term memory enhancement by a class of broad-acting drugs known as histone deacetylase (HDAC) inhibitors. Understanding the molecular mechanisms that regulate these genes and identifying ways to increase their activity may provide novel therapeutic approaches for ameliorating cognitive dysfunction. In the present study, we find that Nr4a gene expression after learning requires the cAMP-response element binding (CREB) interaction domain of the histone acetyltransferase CREB-binding protein (CBP)...
December 7, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27820700/the-transcription-factor-nr4a3-controls-cd103-dendritic-cell-migration
#12
Kiwon Park, Zbigniew Mikulski, Goo-Young Seo, Aleksander Y Andreyev, Paola Marcovecchio, Amy Blatchley, Mitchell Kronenberg, Catherine C Hedrick
The transcription factor NR4A3 (also known as NOR-1) is a member of the Nr4a family of nuclear receptors and is expressed in myeloid and lymphoid cells. Here, we have shown that Nr4a3 is essential for the migration of CD103+ dendritic cells (DCs) to lymph nodes (LNs). Nr4a3-deficient mice had very few CD103+ migratory DCs (mDCs) present in LNs, and mixed-chimera studies revealed that this migratory defect was cell intrinsic. We further found that CD103+ DCs from Nr4a3-deficient mice displayed a marked loss of surface expression of the chemokine CCR7...
December 1, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27646469/adenovirus-mediated-expression-of-orphan-nuclear-receptor-nr4a2-targeting-hepatic-stellate-cell-attenuates-liver-fibrosis-in-rats
#13
Pengguo Chen, Jie Li, Yan Huo, Jin Lu, Lili Wan, Quanjun Yang, Jinlu Huang, Run Gan, Cheng Guo
Liver fibrosis is a wound-healing response characterized with the accumulation of extracellular matrix (ECM). And hepatic stellate cells (HSCs) are the principal cell source of ECM. NR4A2 (Nurr1) is a member of orphan nuclear receptor NR4A family and acts as transcription factor. It participates in regulating cell differentiation, proliferation and apoptosis. We previously demonstrated that NR4A2 expression in fibrotic liver reduced significantly compared with normal liver and NR4A2 knockout in HSCs promoted ECM production...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27587263/crtc1-function-during-memory-encoding-is-disrupted-in-neurodegeneration
#14
Arnaldo Parra-Damas, Meng Chen, Lilian Enriquez-Barreto, Laura Ortega, Sara Acosta, Judith Camats Perna, M Neus Fullana, José Aguilera, José Rodríguez-Alvarez, Carlos A Saura
BACKGROUND: Associative memory impairment is an early clinical feature of dementia patients, but the molecular and cellular mechanisms underlying these deficits are largely unknown. In this study, we investigated the functional regulation of the cyclic adenosine monophosphate response element binding protein (CREB)-regulated transcription coactivator 1 (CRTC1) by associative learning in physiological and neurodegenerative conditions. METHODS: We evaluated the activation of CRTC1 in the hippocampus of control mice and mice lacking the Alzheimer's disease-linked presenilin genes (presenilin conditional double knockout [PS cDKO]) after one-trial contextual fear conditioning by using biochemical, immunohistochemical, and gene expression analyses...
January 15, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/27515096/decreased-expression-of-nr4a-nuclear-receptors-in-adenomyosis-impairs-endometrial-decidualization
#15
Yue Jiang, Ruiwei Jiang, Xi Cheng, Qun Zhang, Yali Hu, Hui Zhang, Yun Cao, Mei Zhang, Junxia Wang, Lijun Ding, Zhenyu Diao, Haixiang Sun, Guijun Yan
STUDY QUESTION: How do NR4A receptors drive decidualization of human endometrial stromal cells (hESCs)? SUMMARY ANSWER: NR4A receptors modulate endometrial decidualization by transcriptional activation of FOXO1A, and in adenomyosis patients, the reduced expression of NR4A receptors in the eutopic endometrium may represent a novel mechanism to explain impaired decidualization and subfertility. WHAT IS KNOWN ALREADY: A close relationship between impaired decidualization and subfertility has been established...
September 2016: Molecular Human Reproduction
https://www.readbyqxmd.com/read/27435855/nurr1-and-ppar%C3%AE-protect-pc12-cells-against-mpp-toxicity-involvement-of-selective-genes-anti-inflammatory-ros-generation-and-antimitochondrial-impairment
#16
Mohammad Jodeiri Farshbaf, Mahboobeh Forouzanfar, Kamran Ghaedi, Abbas Kiani-Esfahani, Maryam Peymani, Alireza Shoaraye Nejati, Tayebeh Izadi, Khadijeh Karbalaie, Maryam Noorbakhshnia, Soheila Rahgozar, Hossein Baharvand, Mohammad Hossein Nasr-Esfahani
Parkinson's disease (PD) can degenerate dopaminergic (DA) neurons in midbrain, substantia-nigra pars compacta. Alleviation of its symptoms and protection of normal neurons against degeneration are the main aspects of researches to establish novel therapeutic strategies. PPARγ as a member of PPARs have shown neuroprotection in a number of neurodegenerative disorders such as Alzheimer's disease and PD. Nuclear receptor related 1 protein (Nurr1) is, respectively, member of NR4A family and has received great attentions as potential target for development, maintenance, and survival of DA neurons...
September 2016: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/27221116/%C3%AE-cell-deletion-of-nr4a1-and-nr4a3-nuclear-receptors-impedes-mitochondrial-respiration-and-insulin-secretion
#17
Merrick S Reynolds, Chad R Hancock, Jason D Ray, Kyle B Kener, Carrie Draney, Kevin Garland, Jeremy Hardman, Benjamin T Bikman, Jeffery S Tessem
β-Cell insulin secretion is dependent on proper mitochondrial function. Various studies have clearly shown that the Nr4a family of orphan nuclear receptors is essential for fuel utilization and mitochondrial function in liver, muscle, and adipose. Previously, we have demonstrated that overexpression of Nr4a1 or Nr4a3 is sufficient to induce proliferation of pancreatic β-cells. In this study, we examined whether Nr4a expression impacts pancreatic β-cell mitochondrial function. Here, we show that β-cell mitochondrial respiration is dependent on the nuclear receptors Nr4a1 and Nr4a3...
July 1, 2016: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27166283/ap2-nr4a3-transgenic-mice-display-reduced-serum-epinephrine-because-of-increased-catecholamine-catabolism-in-adipose-tissue
#18
R Grace Walton, Xiaolin Zhu, Ling Tian, Elizabeth B Heywood, Jian Liu, Helliner S Hill, Jiarong Liu, Dennis Bruemmer, Qinglin Yang, Yuchang Fu, W Timothy Garvey
The NR4A orphan nuclear receptors function as early response genes to numerous stimuli. Our laboratory has previously demonstrated that overexpression of NR4A3 (NOR-1, MINOR) in 3T3-L1 adipocytes enhances insulin-stimulated glucose uptake. To assess the in vivo effect of NR4A3 on adipocytes, we generated transgenic mice with NR4A3 overexpression driven by the adipocyte fatty acid-binding protein (AP2) promoter (AP2-NR4A3 mice). We hypothesized that AP2-NR4A3 mice would display enhanced glucose tolerance and insulin sensitivity...
July 1, 2016: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27159982/altered-nr4a-subfamily-gene-expression-level-in-peripheral-blood-of-parkinson-s-and-alzheimer-s-disease-patients
#19
Francesca Montarolo, Simona Perga, Serena Martire, Désirée Nicole Navone, Alberto Marchet, Daniela Leotta, Antonio Bertolotto
Parkinson's disease (PD) is a neurodegenerative pathology characterized by the degeneration of midbrain dopamine neurons, whose development and maintenance in brain is related to the transcription factor NR4A2 (also called Nurr1). Notably, NR4A2 is a neuroprotective agent with anti-inflammatory role in microglia and astrocytes. Furthermore, mutations in NR4A2 gene are associated to the familial form of PD, and its gene expression level is down-regulated in blood obtained from PD patients. NR4A2 belongs to the NR4A subfamily consisting of three members: NR4A1, NR4A2, and NR4A3...
October 2016: Neurotoxicity Research
https://www.readbyqxmd.com/read/27128111/identification-of-a-binding-site-for-unsaturated-fatty-acids-in-the-orphan-nuclear-receptor-nurr1
#20
Ian Mitchelle S de Vera, Pankaj K Giri, Paola Munoz-Tello, Richard Brust, Jakob Fuhrmann, Edna Matta-Camacho, Jinsai Shang, Sean Campbell, Henry D Wilson, Juan Granados, William J Gardner, Trevor P Creamer, Laura A Solt, Douglas J Kojetin
Nurr1/NR4A2 is an orphan nuclear receptor, and currently there are no known natural ligands that bind Nurr1. A recent metabolomics study identified unsaturated fatty acids, including arachidonic acid and docosahexaenoic acid (DHA), that interact with the ligand-binding domain (LBD) of a related orphan receptor, Nur77/NR4A1. However, the binding location and whether these ligands bind other NR4A receptors were not defined. Here, we show that unsaturated fatty acids also interact with the Nurr1 LBD, and solution NMR spectroscopy reveals the binding epitope of DHA at its putative ligand-binding pocket...
July 15, 2016: ACS Chemical Biology
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