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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.)
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 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)...
November 4, 2016: Current Topics in Medicinal Chemistry
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
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)...
October 14, 2016: Neurotoxicology and Teratology
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...
July 30, 2016: Oncotarget
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)...
October 3, 2016: In Vitro Cellular & Developmental Biology. Animal
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
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
Karine Mathilde Campestrini Dallagnol, Aline Pertile Remor, Rodrigo Augusto da Silva, Rui Daniel Prediger, Alexandra Latini, Aderbal Silva Aguiar
Exercise improves mental health and synaptic function in the aged brain. However, the molecular mechanisms involved in exercise-induced healthy brain aging are not well understood. Evidence supports the role of neurogenesis and neuroplasticity in exercise-induced neuroplasticity. The gene silencing transcription factor neuronal RE1-silencing transcription factor (REST)/neuron-restrictive silencer factor (NRSF) and an anti-inflammatory role of exercise are also candidate mechanisms. We evaluate the effect of 8 weeks of physical activity on running wheels (RW) on motor and depressive-like behavior and hippocampal gene expression of brain-derived neurotrophic factor (BDNF), REST, and interleukins IL-1β and IL-10 of adult and aged C57BL/6 mice...
July 29, 2016: Brain, Behavior, and Immunity
Nady El Hajj, Marcus Dittrich, Julia Böck, Theo F J Kraus, Indrajit Nanda, Tobias Müller, Larissa Seidmann, Tim Tralau, Danuta Galetzka, Eberhard Schneider, Thomas Haaf
Using Illumina 450K arrays, 1.85% of all analyzed CpG sites were significantly hypermethylated and 0.31% hypomethylated in fetal Down syndrome (DS) cortex throughout the genome. The methylation changes on chromosome 21 appeared to be balanced between hypo- and hyper-methylation, whereas, consistent with prior reports, all other chromosomes showed 3-11 times more hyper- than hypo-methylated sites. Reduced NRSF/REST expression due to upregulation of DYRK1A (on chromosome 21q22.13) and methylation of REST binding sites during early developmental stages may contribute to this genome-wide excess of hypermethylated sites...
August 2, 2016: Epigenetics: Official Journal of the DNA Methylation Society
Jun-Ya Kaimori, Kazumitsu Maehara, Yoko Hayashi-Takanaka, Akihito Harada, Masafumi Fukuda, Satoko Yamamoto, Naotsugu Ichimaru, Takashi Umehara, Shigeyuki Yokoyama, Ryo Matsuda, Tsuyoshi Ikura, Koji Nagao, Chikashi Obuse, Naohito Nozaki, Shiro Takahara, Toshifumi Takao, Yasuyuki Ohkawa, Hiroshi Kimura, Yoshitaka Isaka
Histone acetylation is generally associated with gene activation and chromatin decondensation. Recent mass spectrometry analysis has revealed that histone H4 lysine 20, a major methylation site, can also be acetylated. To understand the function of H4 lysine 20 acetylation (H4K20ac), we have developed a specific monoclonal antibody and performed ChIP-seq analysis using HeLa-S3 cells. H4K20ac was enriched around the transcription start sites (TSSs) of minimally expressed genes and in the gene body of expressed genes, in contrast to most histone acetylation being enriched around the TSSs of expressed genes...
2016: Scientific Reports
Chi Hai-Ying, Kiori Nagano, Sayeh Ezzikouri, Chiho Yamaguchi, Mohammad Enamul Hoque Kayesh, Khadija Rebbani, Bouchra Kitab, Hirohumi Nakano, Hiroyuki Kouji, Michinori Kohara, Kyoko Tsukiyama-Kohara
Previous studies have shown that intermittent cold stress (ICS) induces depression-like behaviors in mammals. Tupaia belangeri (the tree shrew) is the only experimental animal other than the chimpanzee that has been shown to be susceptible to infection by hepatitis B and C viruses. Moreover, full genome sequence analysis has revealed strong homology between host proteins in Tupaia and in humans and other primates. Tupaia neuromodulator receptor proteins are also known to have a high degree of homology with their corresponding primate proteins...
July 29, 2016: Experimental Animals
Gary P Brennan, Deblina Dey, Yuncai Chen, Katelin P Patterson, Eric J Magnetta, Alicia M Hall, Celine M Dube, Yu-Tang Mei, Tallie Z Baram
Insult-provoked transformation of neuronal networks into epileptic ones involves multiple mechanisms. Intervention studies have identified both dysregulated inflammatory pathways and NRSF-mediated repression of crucial neuronal genes as contributors to epileptogenesis. However, it remains unclear how epilepsy-provoking insults (e.g., prolonged seizures) induce both inflammation and NRSF and whether common mechanisms exist. We examined miR-124 as a candidate dual regulator of NRSF and inflammatory pathways. Status epilepticus (SE) led to reduced miR-124 expression via SIRT1--and, in turn, miR-124 repression--via C/EBPα upregulated NRSF...
March 15, 2016: Cell Reports
Solenne Bire, Sophie Casteret, Benoît Piégu, Linda Beauclair, Nathalie Moiré, Peter Arensbuger, Yves Bigot
Transposable elements are driving forces for establishing genetic innovations such as transcriptional regulatory networks in eukaryotic genomes. Here, we describe a silencer situated in the last 300 bp of the Mos1 transposase open reading frame (ORF) which functions in vertebrate and arthropod cells. Functional silencers are also found at similar locations within three other animal mariner elements, i.e. IS630-Tc1-mariner (ITm) DD34D elements, Himar1, Hsmar1 and Mcmar1. These silencers are able to impact eukaryotic promoters monitoring strong, moderate or low expression as well as those of mariner elements located upstream of the transposase ORF...
March 2016: PLoS Genetics
Alix Warburton, Fabio Miyajima, Kanvel Shazadi, Joanne Crossley, Michael R Johnson, Anthony G Marson, Gus A Baker, John P Quinn, Graeme J Sills
Cognitive dysfunction is a common comorbidity in people with epilepsy, but its causes remain unclear. It may be related to the etiology of the disorder, the consequences of seizures, or the effects of antiepileptic drug treatment. Genetics may also play a contributory role. We investigated the influence of variants in the genes encoding neuron-restrictive silencer factor (NRSF) and brain-derived neurotrophic factor (BDNF), proteins previously associated with cognition and epilepsy, on cognitive function in people with newly diagnosed epilepsy...
January 2016: Epilepsy & Behavior: E&B
Kaushali Thakore-Shah, Tasneem Koleilat, Majib Jan, Alan John, April D Pyle
REST (RE1 silencing transcription factor), also known as NRSF (neuron-restrictive silencer factor), is a well-known transcriptional repressor of neural genes in non-neural tissues and stem cells. Dysregulation of REST activity is thought to play a role in diverse diseases including epilepsy, cancer, Down's syndrome and Huntington's disease. The role of REST/NRSF in control of human embryonic stem cell (hESC) fate has never been examined. To evaluate the role of REST in hESCs we developed an inducible REST knockdown system and examined both growth and differentiation over short and long term culture...
2015: PloS One
Dianna E Willis, Meng Wang, Elizabeth Brown, Lilah Fones, John W Cave
Neuropathic pain often develops following nerve injury as a result of maladaptive changes that occur in the injured nerve and along the nociceptive pathways of the peripheral and central nervous systems. Multiple cellular and molecular mechanisms likely account for these changes; however, the exact nature of these mechanisms remain largely unknown. A growing number of studies suggest that alteration in gene expression is an important step in the progression from acute to chronic pain states and epigenetic regulation has been proposed to drive this change in gene expression...
June 20, 2016: Neuroscience Letters
Nora Urraca, Rawaha Memon, Ikbale El-Iyachi, Sarita Goorha, Colleen Valdez, Quynh T Tran, Reese Scroggs, Gustavo A Miranda-Carboni, Martin Donaldson, Dave Bridges, Lawrence T Reiter
A major challenge to the study and treatment of neurogenetic syndromes is accessing live neurons for study from affected individuals. Although several sources of stem cells are currently available, acquiring these involve invasive procedures, may be difficult or expensive to generate and are limited in number. Dental pulp stem cells (DPSCs) are multipotent stem cells that reside deep the pulp of shed teeth. To investigate the characteristics of DPSCs that make them a valuable resource for translational research, we performed a set of viability, senescence, immortalization and gene expression studies on control DPSC and derived neurons...
November 2015: Stem Cell Research
Priya Verma, Rajaneesh K Gupta, Behrose S Gandhi, Poonam Singh
CDRI-08 is a standardized bacoside enriched ethanolic extract of Bacopa monnieri, a nootropic plant. We reported that CDRI-08 attenuated oxidative stress and memory impairment in mice, induced by a flame retardant, PBDE-209. In order to explore the mechanism, present study was designed to examine the role of CDRI-08 on the expression of NMDAR1 (NR1) and the binding of REST/NRSF to NR1 promoter against postnatal exposure of PBDE-209. Male mice pups were orally supplemented with CDRI-08 at the doses of 40, 80, or 120 mg/kg along with PBDE-209 (20 mg/kg) during PND 3-10 and frontal cortex and hippocampus were collected at PND 11 and 60 to study the expression and regulation of NR1 by RT-PCR and electrophoretic mobility shift assay, respectively...
2015: Evidence-based Complementary and Alternative Medicine: ECAM
Sadia Rahman, Mathew J K Jones, Prasad V Jallepalli
The cohesin complex links DNA molecules and plays key roles in the organization, expression, repair, and segregation of eukaryotic genomes. In vertebrates the Esco1 and Esco2 acetyltransferases both modify cohesin's Smc3 subunit to establish sister chromatid cohesion during S phase, but differ in their N-terminal domains and expression during development and across the cell cycle. Here we show that Esco1 and Esco2 also differ dramatically in their interaction with chromatin, as Esco1 is recruited by cohesin to over 11,000 sites, whereas Esco2 is infrequently enriched at REST/NRSF target genes...
September 8, 2015: Proceedings of the National Academy of Sciences of the United States of America
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