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https://www.readbyqxmd.com/read/28596506/by-up-regulating-%C3%AE-and-%C3%AE-opioid-receptors-neuron-restrictive-silencer-factor-knockdown-promotes-neurological-recovery-after-ischemia
#1
Hui-Min Liang, Li-Jiao Geng, Xiao-Yan Shi, Chao-Gang Zhang, Shu-Yan Wang, Guang-Ming Zhang
We investigated the effects of neuron-restrictive silencer factor (NRSF) on proliferation of endogenous nerve stem cells (NSCs) and on μ- and δ-opioid receptor (MOR/DOR) expression in rats after cerebral ischemia. Among 100 rats subjected to cerebral ischemia, 20 rats were transfected with NRSF shRNA, and the remaining 80 were randomly assigned to normal, sham, model, and negative control (NC) groups. On days 7, 14, and 28 after ischemia and reperfusion, neurological function scores were assigned and a step-down passive avoidance test was conducted...
May 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28575744/decreased-neural-precursor-cell-pool-in-nadph-oxidase-2-deficiency-from-mouse-brain-to-neural-differentiation-of-patient-derived-ipsc
#2
Zeynab Nayernia, Marilena Colaianna, Natalia Robledinos-Antón, Eveline Gutzwiller, Frédérique Sloan-Béna, Elisavet Stathaki, Yousef Hibaoui, Antonio Cuadrado, Jürgen Hescheler, Marie-José Stasia, Tomo Saric, Vincent Jaquet, Karl-Heinz Krause
There is emerging evidence for the involvement of reactive oxygen species (ROS) in the regulation of stem cells and cellular differentiation. Absence of the ROS-generating NADPH oxidase NOX2 in chronic granulomatous disease (CGD) patients, predominantly manifests as immune deficiency, but has also been associated with decreased cognition. Here, we investigate the role of NOX enzymes in neuronal homeostasis in adult mouse brain and in neural cells derived from human induced pluripotent stem cells (iPSC). High levels of NOX2 were found in mouse adult neurogenic regions...
April 24, 2017: Redox Biology
https://www.readbyqxmd.com/read/28489825/intratumoural-heterogeneity-generated-by-notch-signalling-promotes-small-cell-lung-cancer
#3
Jing Shan Lim, Alvaro Ibaseta, Marcus M Fischer, Belinda Cancilla, Gilbert O'Young, Sandra Cristea, Vincent C Luca, Dian Yang, Nadine S Jahchan, Cécile Hamard, Martine Antoine, Marie Wislez, Christina Kong, Jennifer Cain, Yu-Wang Liu, Ann M Kapoun, K Christopher Garcia, Timothy Hoey, Christopher L Murriel, Julien Sage
The Notch signalling pathway mediates cell fate decisions and is tumour suppressive or oncogenic depending on the context. During lung development, Notch pathway activation inhibits the differentiation of precursor cells to a neuroendocrine fate. In small-cell lung cancer, an aggressive neuroendocrine lung cancer, loss-of-function mutations in NOTCH genes and the inhibitory effects of ectopic Notch activation indicate that Notch signalling is tumour suppressive. Here we show that Notch signalling can be both tumour suppressive and pro-tumorigenic in small-cell lung cancer...
May 10, 2017: Nature
https://www.readbyqxmd.com/read/28464229/functional-characterization-of-the-neuron-restrictive-silencer-element-in-the-human-tryptophan-hydroxylase-2-gene-expression
#4
Yukino Nawa, Hanae Kaneko, Masayuki Oda, Masaaki Tsubonoya, Tomoko Hiroi, Maria Teresa Gentile, Luca Colucci-D'Amato, Ryoya Takahashi, Hiroaki Matsui
Tryptophan hydroxylase 2 (TPH2) is the key enzyme in the synthesis of neuronal serotonin. Although previous studies suggest that TPH2 NRSE (neuron-restrictive silencer element) functions as a negative regulator dependent on NRSF (neuron-restrictive silencer factor) activity, the underlying mechanisms are yet to be fully elucidated. Here, we show a detailed analysis of the NRSE-mediated repression of the human TPH2 (hTPH2) promoter activity in RN46A cells, a cell line derived from rat raphe neurons. Quantitative real-time RT-PCR analysis revealed the expression of serotonergic marker genes (Mash1, Nkx2...
May 2, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28415063/neuron-restrictive-silencer-factor-mediated-downregulation-of-%C3%AE-opioid-receptor-contributes-to-the-reduced-morphine-analgesia-in-bone-cancer-pain
#5
Chao Zhu, Jun Tang, Tan Ding, Lei Chen, Wei Wang, Xiao-Peng Mei, Xiao-Tao He, Wen Wang, Li-Dong Zhang, Yu-Lin Dong, Zhuo-Jing Luo
Bone cancer pain has been reported to have unique mechanisms and is resistant to morphine treatment. Recent studies have indicated that neuron-restrictive silencer factor (NRSF) plays a crucial role in modulating the expression of the μ-opioid receptor (MOR) gene. The present study elucidates the regulatory mechanisms of MOR and its ability to affect bone cancer pain. Using a sarcoma-inoculated murine model, pain behaviors that represent continuous or breakthrough pain were evaluated. Expression of NRSF in the dorsal root ganglion (DRG) and spinal dorsal horn was quantified at the transcriptional and translational levels, respectively...
May 2017: Pain
https://www.readbyqxmd.com/read/28275159/enduring-memory-impairments-provoked-by-developmental-febrile-seizures-are-mediated-by-functional-and-structural-effects-of-neuronal-restrictive-silencing-factor
#6
Katelin P Patterson, Jeremy M Barry, Megan M Curran, Akanksha Singh-Taylor, Gary Brennan, Neggy Rismanchi, Matias Page, Yoav Noam, Gregory L Holmes, Tallie Z Baram
In a subset of children experiencing prolonged febrile seizures (FSs), the most common type of childhood seizures, cognitive outcomes are compromised. However, the underlying mechanisms are unknown. Here we identified significant, enduring spatial memory problems in male rats following experimental prolonged FS (febrile status epilepticus; eFSE). Remarkably, these deficits were abolished by transient, post hoc interference with the chromatin binding of the transcriptional repressor neuron restrictive silencing factor (NRSF or REST)...
April 5, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28218430/stepwise-assembly-of-functional-c-terminal-rest-nrsf-transcriptional-repressor-complexes-as-a-drug-target
#7
Ken Inui, Zongpei Zhao, Juan Yuan, Sakthidasan Jayaprakash, Le T M Le, Srdja Drakulic, Bjoern Sander, Monika M Golas
In human cells, thousands of predominantly neuronal genes are regulated by the repressor element 1 (RE1)-silencing transcription factor/neuron-restrictive silencer factor (REST/NRSF). REST/NRSF represses transcription of these genes in stem cells and non-neuronal cells by tethering corepressor complexes. Aberrant REST/NRSF expression and intracellular localization are associated with cancer and neurodegeneration in humans. To date, detailed molecular analyses of REST/NRSF and its C-terminal repressor complex have been hampered largely by the lack of sufficient amounts of purified REST/NRSF and its complexes...
May 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28197553/the-role-of-sirt1-in-epileptogenesis
#8
Alicia M Hall, Gary P Brennan, Tiffany M Nguyen, Akanksha Singh-Taylor, Hyun-Seung Mun, Mary J Sargious, Tallie Z Baram
The mechanisms by which brain insults lead to subsequent epilepsy remain unclear. Insults, including trauma, stroke, tumors, infections, and long seizures [status epilepticus (SE)], create a neuronal state of increased metabolic demand or decreased energy supply. Neurons express molecules that monitor their metabolic state, including sirtuins (Sirts). Sirtuins deacetylate cytoplasmic proteins and nuclear histones, and their epigenetic modulation of the chromatin governs the expression of many genes, influencing neuronal properties...
January 2017: ENeuro
https://www.readbyqxmd.com/read/28070121/nrsf-dependent-epigenetic-mechanisms-contribute-to-programming-of-stress-sensitive-neurons-by-neonatal-experience-promoting-resilience
#9
A Singh-Taylor, J Molet, S Jiang, A Korosi, J L Bolton, Y Noam, K Simeone, J Cope, Y Chen, A Mortazavi, T Z Baram
Resilience to stress-related emotional disorders is governed in part by early-life experiences. Here we demonstrate experience-dependent re-programming of stress-sensitive hypothalamic neurons, which takes place through modification of neuronal gene expression via epigenetic mechanisms. Specifically, we found that augmented maternal care reduced glutamatergic synapses onto stress-sensitive hypothalamic neurons and repressed expression of the stress-responsive gene, Crh. In hypothalamus in vitro, reduced glutamatergic neurotransmission recapitulated the repressive effects of augmented maternal care on Crh, and this required recruitment of the transcriptional repressor repressor element-1 silencing transcription factor/neuron restrictive silencing factor (NRSF)...
January 10, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28008994/common-germline-variants-within-the-cdkn2a-2b-region-affect-risk-of-pancreatic-neuroendocrine-tumors
#10
Daniele Campa, Gabriele Capurso, Manuela Pastore, Renata Talar-Wojnarowska, Anna Caterina Milanetto, Luca Landoni, Evaristo Maiello, Rita T Lawlor, Ewa Malecka-Panas, Niccola Funel, Maria Gazouli, Antonio De Bonis, Harald Klüter, Maria Rinzivillo, Gianfranco Delle Fave, Thilo Hackert, Stefano Landi, Peter Bugert, Franco Bambi, Livia Archibugi, Aldo Scarpa, Verena Katzke, Christos Dervenis, Valbona Liço, Sara Furlanello, Oliver Strobel, Francesca Tavano, Daniela Basso, Rudolf Kaaks, Claudio Pasquali, Manuel Gentiluomo, Cosmeri Rizzato, Federico Canzian
Pancreatic neuroendocrine tumors (PNETs) are heterogeneous neoplasms which represent only 2% of all pancreatic neoplasms by incidence, but 10% by prevalence. Genetic risk factors could have an important role in the disease aetiology, however only a small number of case control studies have been performed yet. To further our knowledge, we genotyped 13 SNPs belonging to the pleiotropic CDKN2A/B gene region in 320 PNET cases and 4436 controls, the largest study on the disease so far. We observed a statistically significant association between the homozygotes for the minor allele of the rs2518719 SNP and an increased risk of developing PNET (ORhom = 2...
December 23, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27976729/interactomic-analysis-of-rest-nrsf-and-implications-of-its-functional-links-with-the-transcription-suppressor-trim28-during-neuronal-differentiation
#11
Namgyu Lee, Sung Jin Park, Ghazal Haddad, Dae-Kyum Kim, Seon-Min Park, Sang Ki Park, Kwan Yong Choi
RE-1 silencing transcription factor (REST) is a transcriptional repressor that regulates gene expression by binding to repressor element 1. However, despite its critical function in physiology, little is known about its interaction proteins. Here we identified 204 REST-interacting proteins using affinity purification and mass spectrometry. The interactome included proteins associated with mRNA processing/splicing, chromatin organization, and transcription. The interactions of these REST-interacting proteins, which included TRIM28, were confirmed by co-immunoprecipitation and immunocytochemistry, respectively...
December 15, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27956497/non-cpg-methylation-by-dnmt3b-facilitates-rest-binding-and-gene-silencing-in-developing-mouse-hearts
#12
Donghong Zhang, Bingruo Wu, Ping Wang, Yidong Wang, Pengfei Lu, Tamilla Nechiporuk, Thomas Floss, John M Greally, Deyou Zheng, Bin Zhou
The dynamic interaction of DNA methylation and transcription factor binding in regulating spatiotemporal gene expression is essential for embryogenesis, but the underlying mechanisms remain understudied. In this study, using mouse models and integration of in vitro and in vivo genetic and epigenetic analyses, we show that the binding of REST (repressor element 1 (RE1) silencing transcription factor; also known as NRSF) to its cognate RE1 sequences is temporally regulated by non-CpG methylation. This process is dependent on DNA methyltransferase 3B (DNMT3B) and leads to suppression of adult cardiac genes in developing hearts...
April 7, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/27900343/divergence-and-rewiring-of-regulatory-networks-for-neural-development-between-human-and-other-species
#13
COMMENT
Ping Wang, Dejian Zhao, Shira Rockowitz, Deyou Zheng
Neural and brain development in human and other mammalian species are largely similar, but distinct features exist at the levels of macrostructure and underlying genetic control. Comparative studies of epigenetic regulation and transcription factor (TF) binding in humans, chimpanzees, rodents, and other species have found large differences in gene regulatory networks. A recent analysis of the cistromes of REST/NRSF, a critical transcriptional regulator for the nervous system, demonstrated that REST binding to syntenic genomic regions (i...
2016: Neurogenesis (Austin, Tex.)
https://www.readbyqxmd.com/read/27823568/pharmacological-histone-deacetylation-distinguishes-transcriptional-regulators
#14
Haloom Rafehi, Tom C Karagiannis, Assam El-Osta
INTRODUCTION: Histone deacetylase (HDAC) enzymes control the acetylation status of transcription factors that regulate chromatin structure and gene function. The transcriptional regulatory factors that distinguish histone acetylation and deacetylation patterns by pharmacological HDAC inhibition (HDACi) have not yet been studied. METHODS: We analysed sequencing datasets derived from human aortic endothelial cells (HAECs) stimulated with the HDAC inhibitors, Trichostatin A (TSA) and suberoylanilide hydroxamic acid (SAHA)...
2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/27762075/sex-specific-linkage-scans-in-opioid-dependence
#15
Bao-Zhu Yang, Shizhong Han, Henry R Kranzler, Abraham A Palmer, Joel Gelernter
Sex influences risk for opioid dependence (OD). We hypothesized that sex might interact with genetic loci that influence the risk for OD. Therefore we performed an analysis to identify sex-specific genomic susceptibility regions for OD using linkage. Over 6,000 single nucleotide polymorphism (SNP) markers were genotyped for 1,758 African- and European-American (AA and EA) individuals from 739 families, ascertained via affected sib-pairs with OD and/or cocaine dependence. Autosomewide non-parametric linkage scans, stratified by sex and population, were performed...
October 20, 2016: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
https://www.readbyqxmd.com/read/27751817/prenatal-arsenic-exposure-alters-rest-nrsf-and-microrna-regulators-of-embryonic-neural-stem-cell-fate-in-a-sex-dependent-manner
#16
Christina R Tyler, Matthew T Labrecque, Elizabeth R Solomon, Xun Guo, Andrea M Allan
Exposure to arsenic, a common environmental toxin found in drinking water, leads to a host of neurological pathologies. We have previously demonstrated that developmental exposure to a low level of arsenic (50ppb) alters epigenetic processes that underlie deficits in adult hippocampal neurogenesis leading to aberrant behavior. It is unclear if arsenic impacts the programming and regulation of embryonic neurogenesis during development when exposure occurs. The master negative regulator of neural-lineage, REST/NRSF, controls the precise timing of fate specification and differentiation of neural stem cells (NSCs)...
January 2017: Neurotoxicology and Teratology
https://www.readbyqxmd.com/read/27732941/negative-regulation-of-rest-on-nr2b-in-spinal-cord-contributes-to-the-development-of-bone-cancer-pain-in-mice
#17
Dan Wang, Jianbo Yu
In this study, C3H/HeNCrlVr mice are implanted with sarcoma NCTC 2472 cells into the intramedullary space of the femur to induce ongoing bone cancer-related pain behaviors. During the progress of the bone cancer pain, the down-regulation in spinal REST (Neuron-restrictive silencer factor, NRSF/REST) with concomitant up-regulation in spinal NR2B (2B subunit of N-methyl-D-aspartate receptor, NR2B) protein expression are observed at days 5, 7, 10 and 14 post-inoculation. Immunofluorescence assay shows that almost all of REST and NR2B-positive signals encompass NeuN (neuron-specific nuclear protein, a neuronal marker)-positive signals in spinal cord of sham and tumor-bearing mice...
December 20, 2016: Oncotarget
https://www.readbyqxmd.com/read/27699654/in-vitro-reprogramming-of-rat-bmmscs-into-pancreatic-endocrine-like-cells
#18
Hong-Tu Li, Fang-Xu Jiang, Ping Shi, Tao Zhang, Xiao-Yu Liu, Xue-Wen Lin, Zhong-Yan San, Xi-Ning Pang
Islet transplantation provides curative treatments to patients with type 1 diabetes, but donor shortage restricts the broad use of this therapy. Thus, generation of alternative transplantable cell sources is intensively investigated worldwide. We previously showed that bone marrow-derived mesenchymal stem cells (bmMSCs) can be reprogrammed to pancreatic-like cells through simultaneously forced suppression of Rest/Nrsf (repressor element-1 silencing transcription factor/neuronal restrictive silencing factor) and Shh (sonic hedgehog) and activation of Pdx1 (pancreas and duodenal transcription factor 1)...
February 2017: In Vitro Cellular & Developmental Biology. Animal
https://www.readbyqxmd.com/read/27631609/disruption-of-rest-leads-to-the-early-onset-of-cataracts-with-the-aberrant-terminal-differentiation-of-lens-fiber-cells
#19
Hitomi Aoki, Hajime Ogino, Hiroyuki Tomita, Akira Hara, Takahiro Kunisada
REST (RE1-silencing transcription factor, also called Nrsf) is involved in the maintenance of the undifferentiated state of neuronal stem/progenitor cells in vitro by preventing precocious expression of neuronal genes. REST expression was then decreased in developing neurons to down-regulate neuronal genes which allow their maturation. However, the function of REST during neurogenesis in vivo remains to be elucidated because of the early embryonic lethal phenotype of conventional Rest knockout mice. In order to investigate the role of REST in ocular tissues, we generated and examined the mice evoking genetic ablation to Rest specifically to neural tissues including ocular tissue...
2016: PloS One
https://www.readbyqxmd.com/read/27605615/maternal-rest-nrsf-regulates-zebrafish-behavior-through-snap25a-b
#20
Cara E Moravec, John Samuel, Wei Weng, Ian C Wood, Howard I Sirotkin
UNLABELLED: During embryonic development, regulation of gene expression is key to creating the many subtypes of cells that an organism needs throughout its lifetime. Recent work has shown that maternal genetics and environmental factors have lifelong consequences on diverse processes ranging from immune function to stress responses. The RE1-silencing transcription factor (Rest) is a transcriptional repressor that interacts with chromatin-modifying complexes to repress transcription of neural-specific genes during early development...
September 7, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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