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https://www.readbyqxmd.com/read/28218430/stepwise-assembly-of-functional-c-terminal-rest-nrsf-transcriptional-repressor-complexes-as-a-drug-target
#1
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...
February 20, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28197553/the-role-of-sirt1-in-epileptogenesis
#2
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/28142142/the-rs1277306-variant-of-the-rest-gene-confers-susceptibility-to-cognitive-aging-in-an-elderly-taiwanese-population
#3
Eugene Lin, Shih-Jen Tsai, Po-Hsiu Kuo, Yu-Li Liu, Albert C Yang, Chung-Feng Kao, Cheng-Hung Yang
BACKGROUND/AIMS: There is growing evidence that the RE1-silencing transcription factor (REST) gene may contribute to cognitive aging and Alzheimer diseases. In this replication study, we reassessed whether single nucleotide polymorphisms (SNPs) within the REST gene are linked with cognitive aging independently and/or through complex interactions in an older Taiwanese population. METHODS: A total of 634 Taiwanese subjects aged over 60 years from the Taiwan Biobank were analyzed...
February 1, 2017: Dementia and Geriatric Cognitive Disorders
https://www.readbyqxmd.com/read/28122430/exosome-based-delivery-of-mir-124-in-a-huntington-s-disease-model
#4
Soon-Tae Lee, Wooseok Im, Jae-Jun Ban, Mijung Lee, Keun-Hwa Jung, Sang Kun Lee, Kon Chu, Manho Kim
OBJECTIVE: Huntington's disease (HD) is a genetic neurodegenerative disease that is caused by abnormal CAG expansion. Altered microRNA (miRNA) expression also causes abnormal gene regulation in this neurodegenerative disease. The delivery of abnormally downregulated miRNAs might restore normal gene regulation and have a therapeutic effect. METHODS: We developed an exosome-based delivery method to treat this neurodegenerative disease. miR-124, one of the key miRNAs that is repressed in HD, was stably overexpressed in a stable cell line...
January 2017: Journal of Movement Disorders
https://www.readbyqxmd.com/read/28049845/rest-corepressors-rcor1-and-rcor2-and-the-repressor-insm1-regulate-the-proliferation-differentiation-balance-in-the-developing-brain
#5
Caitlin E Monaghan, Tamilla Nechiporuk, Sophia Jeng, Shannon K McWeeney, Jianxun Wang, Michael G Rosenfeld, Gail Mandel
The transcriptional events that lead to the cessation of neural proliferation, and therefore enable the production of proper numbers of differentiated neurons and glia, are still largely uncharacterized. Here, we report that the transcription factor Insulinoma-associated 1 (INSM1) forms complexes with RE1 Silencing Transcription factor (REST) corepressors RCOR1 and RCOR2 in progenitors in embryonic mouse brain. Mice lacking both RCOR1 and RCOR2 in developing brain die perinatally and generate an abnormally high number of neural progenitors at the expense of differentiated neurons and oligodendrocyte precursor cells...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28040710/rest-represses-mir-124-and-mir-203-to-regulate-distinct-oncogenic-properties-of-glioblastoma-stem-cells
#6
Anantha L Marisetty, Sanjay K Singh, Tran N Nguyen, Cristian Coarfa, Bin Liu, Sadhan Majumder
BACKGROUND: Glioblastoma (GBM) is one of the most common, aggressive, and invasive human brain tumors. There are few reliable mechanism-based therapeutic approaches for GBM patients. The transcriptional repressor RE1 silencing transcriptional factor (REST) regulates the oncogenic properties of a class of GBM stem-like cells (high-REST [HR]-GSCs) in humans. However, it has been unclear whether REST represses specific targets to regulate specific oncogenic functions or represses all targets with overlapping functions in GSCs...
December 31, 2016: Neuro-oncology
https://www.readbyqxmd.com/read/27956636/accomplishing-simple-solubility-based-separations-of-rare-earth-elements-with-complexes-bearing-size-sensitive-molecular-apertures
#7
Justin A Bogart, Bren E Cole, Michael A Boreen, Connor A Lippincott, Brian C Manor, Patrick J Carroll, Eric J Schelter
Rare earth (RE) metals are critical components of electronic materials and permanent magnets. Recycling of consumer materials is a promising new source of rare REs. To incentivize recycling, there is a clear need for the development of simple methods for targeted separations of mixtures of RE metal salts. Metal complexes of a tripodal hydroxylaminato ligand, TriNOx(3-), featured a size-sensitive aperture formed of its three η(2)-(N,O) ligand arms. Exposure of cations in the aperture induced a self-associative equilibrium comprising RE(TriNOx)THF and [RE(TriNOx)]2 species...
December 27, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27956497/non-cpg-methylation-by-dnmt3b-facilitates-rest-binding-and-gene-silencing-in-developing-mouse-hearts
#8
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...
December 11, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27940549/repression-of-telomerase-gene-promoter-requires-human-specific-genomic-context-and-is-mediated-by-multiple-hdac1-containing-corepressor-complexes
#9
De Cheng, Yuanjun Zhao, Shuwen Wang, Fan Zhang, Mariano Russo, Steven B McMahon, Jiyue Zhu
The human telomerase reverse transcriptase (hTERT) gene is repressed in most somatic cells, whereas the expression of the mouse mTert gene is widely detected. To understand the mechanisms of this human-specific repression, we constructed bacterial artificial chromosome (BAC) reporters using human and mouse genomic DNAs encompassing the TERT genes and neighboring loci. Upon chromosomal integration, the hTERT, but not the mTert, reporter was stringently repressed in telomerase-negative human cells in a histone deacetylase (HDAC)-dependent manner, replicating the expression of their respective endogenous genes...
December 9, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27748809/decreased-expression-of-mir%C3%A2-9-due-to-e50k%C3%A2-optn-mutation-causes-disruption-of-the-expression-of-bdnf-leading-to-rgc%C3%A2-5-cell-apoptosis
#10
Bo Jiang, Lin Gao, Dawei Lei, Jiannan Liu, Zhengbo Shao, Xinrong Zhou, Renke Li, Donglai Wu, Fei Xue, Yuanmao Zhu, Huiping Yuan
The aims of the present study were to investigate the effect of E50K optineurin (OPTN) mutation on RGC‑5 cells and to define the role of microRNA‑9 (miR‑9) in this system. Transfected RGC‑5 cells were used to evaluate the effects of E50K OPTN on the expression of miR‑9 and subsequent disruption of RGC‑5 cell apoptosis was analyzed using western blotting. The results showed that the expression of E50K OPTN was associated with a marked reduction in the levels of miR‑9 in the E50K OPTN‑transfected RGC‑5 cells...
November 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27685921/expression-profiling-of-re1-silencing-transcription-factor-rest-rest-corepressor-1-rcor1-and-synapsin-1-syn1-genes-in-human-gliomas
#11
Musteyde Yucebas, Sunde Yilmaz Susluer, Hasan Onur Caglar, Tugce Balci, Z Ozlem Dogan Sigva, Taner Akalin, Nezih Oktar, Tayfun Dalbasti, Cigir Biray Avci, Cumhur Gunduz
PURPOSE: The repressor element 1 (RE-1) silencing transcription factor (REST) is a transcription factor which represses the expression of neuronal differentiation-related genes including SYN1 gene. CoREST, encoded by RCOR1 gene, binds to the REST protein for remodeling of chromatin structure. Although there is a relation among REST, RCOR1, and SYN1 genes, the role of these genes in glioma tumors is still unclear. In this study, expressions of REST, RCOR1, and SYN1 genes were detected in primary cultures derived from tumor samples of diffuse astrocytoma (DA), anaplastic oligodendroglioma (AO), and glioblastoma multiforme (GBM) cases...
July 2016: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
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
#12
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
#13
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
https://www.readbyqxmd.com/read/27585404/%C3%AE-re1-xbixb3o6-re-sm-eu-gd-tb-dy-ho-er-y-bi-3-substitution-induced-formation-of-metastable-rare-earth-borates-at-ambient-pressure
#14
Xiaorui Sun, Ruirui Yang, Rixiang Song, Song Leng, Pengfei Jiang, Wenliang Gao, Rihong Cong, Tao Yang
There emerge great interests in the syntheses of metastable polyborates; however, most are involved with the high-pressure technique. A facile method to synthesize metastable rare earth borates at ambient pressure is eagerly required for the large-scale production and property investigation. Here we demonstrate the critical role of Bi(3+) substitutions in the stabilization of metastable β-REB3O6 (RE = Sm, Eu, Gd, Tb, Dy, Ho, Er, and Y) at ambient pressure, where the Bi(3+)-to-RE(3+) substitutions would efficiently reduce the synthetic temperatures to 735-820 °C, well below the upper limit of thermodynamically stable window (840-980 °C)...
September 19, 2016: Inorganic Chemistry
https://www.readbyqxmd.com/read/27544757/down-regulation-of-neuronal-l1-cell-adhesion-molecule-expression-alleviates-inflammatory-neuronal-injury
#15
Lutz Menzel, Magdalena Paterka, Stefan Bittner, Robin White, Wiesia Bobkiewicz, Jack van Horssen, Melitta Schachner, Esther Witsch, Tanja Kuhlmann, Frauke Zipp, Michael K E Schäfer
In multiple sclerosis (MS), the immune cell attack leads to axonal injury as a major cause for neurological disability. Here, we report a novel role of the cell adhesion molecule L1 in the crosstalk between the immune and nervous systems. L1 was found to be expressed by CNS axons of MS patients and human T cells. In MOG35-55-induced murine experimental neuroinflammation, CD4(+) T cells were associated with degenerating axons in the spinal cord, both expressing L1. However, neuronal L1 expression in the spinal cord was reduced, while levels of the transcriptional repressor REST (RE1-Silencing Transcription Factor) were up-regulated...
November 2016: Acta Neuropathologica
https://www.readbyqxmd.com/read/27477921/running-for-rest-physical-activity-attenuates-neuroinflammation-in-the-hippocampus-of-aged-mice
#16
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 neurotrophins 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 8weeks 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
https://www.readbyqxmd.com/read/27364459/the-translationally-relevant-mouse-model-of-the-15q13-3-microdeletion-syndrome-reveals-deficits-in-neuronal-spike-firing-matching-clinical-neurophysiological-biomarkers-seen-in-schizophrenia
#17
Jonas Thelin, Pär Halje, Jacob Nielsen, Michael Didriksen, Per Petersson, Jesper F Bastlund
AIM: To date, the understanding and development of novel treatments for mental illness is hampered by inadequate animal models. For instance, it is unclear to what extent commonly used behavioural tests in animals can inform us on the mental and affective aspects of schizophrenia. METHODS: In order to link pathophysiological processes in an animal model to clinical findings, we have here utilized the recently developed Df(h15q13)/+ mouse model for detailed investigations of cortical neuronal engagement during pre-attentive processing of auditory information from two back-translational auditory paradigms...
July 1, 2016: Acta Physiologica
https://www.readbyqxmd.com/read/27258257/mir-218-involvement-in-cardiomyocyte-hypertrophy-is-likely-through-targeting-rest
#18
Jing-Jing Liu, Cui-Mei Zhao, Zhi-Gang Li, Yu-Mei Wang, Wei Miao, Xiu-Juan Wu, Wen-Jing Wang, Chang Liu, Duo Wang, Kang Wang, Li Li, Lu-Ying Peng
MicroRNAs (miRNAs) have been identified as key players in cardiomyocyte hypertrophy, which is associated with significant risks of heart failure. However, many microRNAs are still not recognized for their functions in pathophysiological processes. In this study, we evaluated effects of miR-218 in cardiomyocyte hypertrophy using both in vitro and in vivo models. We found that miR-218 was evidently downregulated in a transverse aortic constriction (TAC) mouse model. Overexpression of miR-218 is sufficient to reduce hypertrophy, whereas the suppression of miR-218 aggravates hypertrophy in primary cardiomyocytes induced by isoprenaline (ISO)...
May 31, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27180064/srrm4-drives-neuroendocrine-transdifferentiation-of-prostate-adenocarcinoma-under-androgen-receptor-pathway-inhibition
#19
Yinan Li, Nilgun Donmez, Cenk Sahinalp, Ning Xie, Yuwei Wang, Hui Xue, Fan Mo, Himisha Beltran, Martin Gleave, Yuzhuo Wang, Colin Collins, Xuesen Dong
BACKGROUND: Neuroendocrine prostate cancer (NEPC) is an aggressive subtype of castration-resistant prostate cancer that typically does not respond to androgen receptor pathway inhibition (ARPI), and its diagnosis is increasing. OBJECTIVE: To understand how NEPC develops and to identify driver genes to inform therapy for NEPC prevention. DESIGN, SETTING, AND PARTICIPANTS: Whole-transcriptome sequencing data were extracted from prostate tumors from two independent cohorts: The Beltran cohort contained 27 adenocarcinoma and five NEPC patient samples, and the Vancouver Prostate Centre cohort contained three patient samples and nine patient-derived xenografts...
January 2017: European Urology
https://www.readbyqxmd.com/read/27126323/lithium-induced-neuroprotection-in-stroke-involves-increased-mir-124-expression-reduced-re1-silencing-transcription-factor-abundance-and-decreased-protein-deubiquitination-by-gsk3%C3%AE-inhibition-independent-pathways
#20
Thorsten R Doeppner, Britta Kaltwasser, Eduardo H Sanchez-Mendoza, Ahmet B Caglayan, Mathias Bähr, Dirk M Hermann
Lithium promotes acute poststroke neuronal survival, which includes mechanisms that are not limited to GSK3β inhibition. However, whether lithium induces long-term neuroprotection and enhanced brain remodeling is unclear. Therefore, mice were exposed to transient middle cerebral artery occlusion and lithium (1 mg/kg bolus followed by 2 mg/kg/day over up to 7 days) was intraperitoneally administered starting 0-9 h after reperfusion onset. Delivery of lithium no later than 6 h reduced infarct volume on day 2 and decreased brain edema, leukocyte infiltration, and microglial activation, as shown by histochemistry and flow cytometry...
April 28, 2016: Journal of Cerebral Blood Flow and Metabolism
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