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https://www.readbyqxmd.com/read/29902467/correcting-deregulated-fxyd1-expression-rescues-deficits-in-neuronal-arborization-and-potassium-homeostasis-in-mecp2-deficient-male-mice
#1
Valerie Matagne, Joyce Wondolowski, Matthew Frerking, Mohammad Shahidullah, Nicholas A Delamere, Ursula S Sandau, Sarojini Budden, Sergio R Ojeda
Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in the MECP2 gene. In the absence of MeCP2/MECP2, expression of FXYD domain-containing transport regulator 1 (FXYD1) is deregulated in the frontal cortex (FC) of mice and humans. Because FXYD1 is a membrane protein that controls cell excitability by modulating Na+ , K+ -ATPase activity (NKA), an excess of FXYD1 may reduce NKA activity and contribute to the neuronal phenotype of Mecp2 deficient (KO) mice. To determine if FXYD1 can rescue these RTT deficits, we studied the male progeny of Fxyd1 null males bred to heterozygous Mecp2 female mice...
June 11, 2018: Brain Research
https://www.readbyqxmd.com/read/29894742/association-of-high-5-hydroxymethylcytosine-levels-with-ten-eleven-translocation-2-overexpression-and-inflammation-in-sj%C3%A3-gren-s-syndrome-patients
#2
Carolina Lagos, Patricia Carvajal, Isabel Castro, Daniela Jara, Sergio González, Sergio Aguilera, María-José Barrera, Andrew F G Quest, Verónica Bahamondes, Claudio Molina, Ulises Urzúa, Marcela A Hermoso, Cecilia Leyton, María-Julieta González
Here, we determined the 5-hydroxymethylcytosine (5hmC), 5-methylcytosine (5mC), Ten Eleven Translocation (TETs), and DNA methyltransferases (DNMTs) levels in epithelial and inflammatory cells of labial salivary glands (LSG) from Sjögren's syndrome (SS)-patients and the effect of cytokines on HSG cells. LSG from SS-patients, controls and HSG cells incubated with cytokines were analysed. Levels of 5mC, 5hmC, DNMTs, TET2 and MeCP2 were assessed by immunofluorescence. In epithelial cells from SS-patients, an increase in TET2, 5hmC and a decrease in 5mC and MeCP2 were observed, additionally, high levels of 5mC and DNMTs and low levels of 5hmC were detected in inflammatory cells...
June 9, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/29860820/-interaction-between-abnormal-expression-of-fragile-histidine-triad-and-methyl-cpg-binding-protein-2-on-cervical-cancerization
#3
Q Yang, Y Li, L Wang, Z C Song, M J Feng, L Ding, J T Wang
Objective: To explore the relationship between abnormal expression of fragile histidine triad (FHIT) gene and methyl-CpG-binding protein 2 (MeCP2) as well as their interaction on cervical cancerization. Methods: A total of 73 patients with cervical squamous cell carcinoma (SCC), 113 patients with cervical intraepithelial neoplasia (CIN Ⅰ, n =45; CINⅡ/Ⅲ, n =68) and 60 women with normal cervix (NC) were included in the study. Real time PCR and Western blot were performed to detect the expression levels of mRNA and protein about FHIT and MeCP2, respectively...
May 10, 2018: Zhonghua Liu Xing Bing Xue za Zhi, Zhonghua Liuxingbingxue Zazhi
https://www.readbyqxmd.com/read/29859319/cocaine-mediated-activation-of-microglia-and-microglial-mecp2-and-bdnf-production
#4
Bianca Cotto, Hongbo Li, Ronald F Tuma, Sara Jane Ward, Dianne Langford
The molecular substrates underlying cocaine reinforcement and addiction have been studied for decades, with a primary focus on signaling molecules involved in modulation of neuronal communication. Brain-derived neurotrophic factor (BDNF) is an important signaling molecule involved in neuronal dendrite and spine modulation. Methyl CpG binding protein 2 (MeCP2) binds to the promoter region of BDNF to negatively regulate its expression and cocaine can recruit MeCP2 to alter the expression of genes such as BDNF that are involved in synaptic plasticity...
May 30, 2018: Neurobiology of Disease
https://www.readbyqxmd.com/read/29847590/experience-dependent-mecp2-expression-in-the-excitatory-cells-of-mouse-visual-thalamus
#5
Yuki Yagasaki, Goichi Miyoshi, Mariko Miyata
Loss or gain of copy number of the gene encoding the transcription factor methyl-CpG-binding protein 2 (MeCP2) leads to neurodevelopmental disorders (Rett and MeCP2 duplication syndrome), indicating that precisely regulated MeCP2 expression during development is critical for mental health. Consistent with this idea, MeCP2 null mutants exhibit synaptic regression in the dorsal lateral geniculate nucleus (dLGN), the visual relay center in the thalamus, a phenotype resembling that of animals reared in the dark during the visual sensitive period...
2018: PloS One
https://www.readbyqxmd.com/read/29846108/microrna-132-controls-water-homeostasis-through-regulating-mecp2-mediated-vasopressin-synthesis
#6
Roel Bijkerk, Christiane Trimpert, Coen van Solingen, Ruben G de Bruin, Barend W Florijn, Sander Kooijman, Rosa van den Berg, Eric P van der Veer, Edwin O W Bredewold, Patrick C N Rensen, Ton J Rabelink, Benjamin D Humphreys, Peter M T Deen, Anton Jan van Zonneveld
Fine-tuning of the body's water balance is regulated by vasopressin (AVP), which induces the expression and apical membrane insertion of aquaporin-2 water channels and subsequent water reabsorption in the kidney. Here we demonstrate that silencing of microRNA-132 in mice causes severe weight loss due to acute diuresis coinciding with increased plasma osmolality, reduced renal total and plasma membrane expression of aquaporin-2 and abrogated increase in AVP levels. Infusion with synthetic AVP fully reversed the antagomir-132 induced diuresis and low-dose intracerebroventricular administration of antagomir-132 similarly caused acute diuresis...
May 30, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29802390/genome-wide-distribution-of-linker-histone-h1-0-is-independent-of-mecp2
#7
Aya Ito-Ishida, Hari Krishna Yamalanchili, Yingyao Shao, Steven A Baker, Laura D Heckman, Laura A Lavery, Ji-Yoen Kim, Laura M Lombardi, Yaling Sun, Zhandong Liu, Huda Y Zoghbi
Previous studies suggested that MeCP2 competes with linker histone H1, but this hypothesis has never been tested in vivo. Here, we performed chromatin immunoprecipitation followed by sequencing (ChIP-seq) of Flag-tagged-H1.0 in mouse forebrain excitatory neurons. Unexpectedly, Flag-H1.0 and MeCP2 occupied similar genomic regions and the Flag-H1.0 binding was not changed upon MeCP2 depletion. Furthermore, mild overexpression of H1.0 did not alter MeCP2 binding, suggesting that the functional binding of MeCP2 and H1...
June 2018: Nature Neuroscience
https://www.readbyqxmd.com/read/29782864/are-dopamine-receptor-and-transporter-changes-in-rett-syndrome-reflected-in-mecp2-deficient-mice
#8
Dean F Wong, Mary E Blue, James R Brašić, Ayon Nandi, Heather Valentine, Kirstie H Stansfield, Olivier Rousset, Genila Bibat, Mary E Yablonski, Michael V Johnston, Albert Gjedde, SakkuBai Naidu
In the present study we tested the claim that the dopaminergic dysfunction of Rett Syndrome (RTT) also occurs in Mecp2-deficient mice that serve as a model of the syndrome. We used positron emission tomography (PET) to image dopamine D2 receptors (D2 R) and transporters (DAT) in women with RTT and in Mecp2-deficient mice, and D1 R and D2 R density was measured in postmortem human tissue by autoradiography. Results showed 1) significantly reduced D2 R density in the striatum of women with RTT compared to control subjects...
May 18, 2018: Experimental Neurology
https://www.readbyqxmd.com/read/29771284/non-cell-autonomous-otx2-homeoprotein-regulates-visual-cortex-plasticity-through-gadd45b-g
#9
Jessica Apulei, Namsuk Kim, Damien Testa, Jérôme Ribot, David Morizet, Clémence Bernard, Laurent Jourdren, Corinne Blugeon, Ariel A Di Nardo, Alain Prochiantz
The non-cell autonomous transfer of OTX2 homeoprotein transcription factor into juvenile mouse cerebral cortex regulates parvalbumin interneuron maturation and critical period timing. By analyzing gene expression in primary visual cortex of wild-type and Otx2+/GFP mice at plastic and nonplastic ages, we identified several putative genes implicated in Otx2-dependent visual cortex plasticity for ocular dominance. Cortical OTX2 infusion in juvenile mice induced Gadd45b/g expression through direct regulation of transcription...
May 16, 2018: Cerebral Cortex
https://www.readbyqxmd.com/read/29770459/identification-of-correlative-shifts-in-indices-of-brain-cholesterol-metabolism-in-the-c57bl6-mecp2-tm1-1bird-mouse-a-model-for-rett-syndrome
#10
Dieter Lütjohann, Adam M Lopez, Jen-Chieh Chuang, Anja Kerksiek, Stephen D Turley
Rett syndrome (RS) is a pervasive neurodevelopmental disorder resulting from loss-of-function mutations in the X-linked gene methyl-Cpg-binding protein 2 (MECP2). Using a well-defined model for RS, the C57BL6/Mecp2 tm1.1Bird mouse, we have previously found a moderate but persistently lower rate of cholesterol synthesis, measured in vivo, in the brains of Mecp2 -/y mice, starting from about the third week after birth. There was no genotypic difference in the total cholesterol concentration throughout the brain at any age...
May 17, 2018: Lipids
https://www.readbyqxmd.com/read/29769330/activity-dependent-aberrations-in-gene-expression-and-alternative-splicing-in-a-mouse-model-of-rett-syndrome
#11
Sivan Osenberg, Ariel Karten, Jialin Sun, Jin Li, Shaun Charkowick, Christy A Felice, Mary Kritzer, Minh Vu Chuong Nguyen, Peng Yu, Nurit Ballas
Rett syndrome (RTT) is a severe neurodevelopmental disorder that affects about 1 in 10,000 female live births. The underlying cause of RTT is mutations in the X-linked gene, methyl-CpG-binding-protein-2 ( MECP2 ); however, the molecular mechanism by which these mutations mediate the RTT neuropathology remains enigmatic. Specifically, although MeCP2 is known to act as a transcriptional repressor, analyses of the RTT brain at steady-state conditions detected numerous differentially expressed genes, while the changes in transcript levels were mostly subtle...
May 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29769162/increased-pregnancy-losses-following-serial-somatic-cell-nuclear-transfer-in-goats
#12
Min Yang, Iuri Perisse, Zhiqiang Fan, Misha Regouski, Mirella Meyer-Ficca, Irina A Polejaeva
Serial cloning by somatic cell nuclear transfer (SCNT) is a critical tool for the expansion of precious transgenic lines or resetting the lifespan of primary transgenic cells for multiple genetic modifications. We successfully produced second-generation cloned goats using donor neonatal fibroblasts from first-generation clones. However, our attempts to produce any third-generation clones failed. SCNT efficiency decreased progressively with the clonal generations. The rate of pregnancy loss was significantly greater in recloning groups (P<0...
May 17, 2018: Reproduction, Fertility, and Development
https://www.readbyqxmd.com/read/29765857/dna-methylation-and-adult-neurogenesis
#13
REVIEW
Emily M Jobe, Xinyu Zhao
The role of DNA methylation in brain development is an intense area of research because the brain has particularly high levels of CpG and mutations in many of the proteins involved in the establishment, maintenance, interpretation, and removal of DNA methylation impact brain development and/or function. These include DNA methyltransferase (DNMT), Ten-Eleven Translocation (TET), and Methyl-CpG binding proteins (MBPs). Recent advances in sequencing breadth and depth as well the detection of different forms of methylation have greatly expanded our understanding of the diversity of DNA methylation in the brain...
November 9, 2017: Brain Plasticity
https://www.readbyqxmd.com/read/29760177/epigenetic-promoter-dna-methylation-of-mir-124-promotes-hiv-1-tat-mediated-microglial-activation-via-mecp2-stat3-axis
#14
Palsamy Periyasamy, Annadurai Thangaraj, Ming-Lei Guo, Guoku Hu, Shannon Callen, Shilpa Buch
The present study demonstrates HIV-1 Tat-mediated epigenetic downregulation of microglial miR-124 and its association with microglial activation. Exposure of mouse primary microglia isolated from newborn pups of either sex to HIV-1 Tat resulted in decreased expression of primary miR-124-1, primary miR-124-2 as well as the mature miR-124. In parallel, HIV-1 Tat exposure to mouse primary microglial cells resulted in increased expression of DNA methylation enzymes, such as DNMT1, DNMT3A, and DNMT3B that were also accompanied by increased global DNA methylation...
May 14, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29760157/methyl-cpg-binding-protein-2-mediates-antifibrotic-effects-in-scleroderma-fibroblasts
#15
Ye He, Pei-Suen Tsou, Dinesh Khanna, Amr H Sawalha
OBJECTIVE: Emerging evidence supports a role for epigenetic regulation in the pathogenesis of scleroderma (SSc). We aimed to assess the role of methyl-CpG-binding protein 2 (MeCP2), a key epigenetic regulator, in fibroblast activation and fibrosis in SSc. METHODS: Dermal fibroblasts were isolated from patients with diffuse cutaneous SSc (dcSSc) and from healthy controls. MeCP2 expression was measured by qPCR and western blot. Myofibroblast differentiation was evaluated by gel contraction assay in vitro...
May 14, 2018: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/29750041/peptide-sa12-inhibits-proliferation-of-breast-cancer-cell-lines-mcf-7-and-mda-mb-231-through-g0-g1-phase-cell-cycle-arrest
#16
Longfei Yang, Huanran Liu, Min Long, Xi Wang, Fang Lin, Zhaowei Gao, Huizhong Zhang
Background: Targeted therapies have been proven as promising in the treatment of breast cancer and have improved survival and quality of life in advanced breast cancer. We previously identified a novel peptide SA12 which showed significant activity in the inhibition of proliferation and induction of apoptosis in SKBr-3 cells. Methods: The present study investigated the potential antitumor role of SA12 in breast cancer cell lines MDA-MB-231 and MCF-7 through Cell Counting Kit-8 assay and colony formation assay, and examined the cell cycle distribution using flow cytometry analysis...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29742424/inhibition-of-gsk3b-reduces-nfkb1-signaling-and-rescues-synaptic-activity-to-improve-the-rett-syndrome-phenotype-in-mecp2-knockout-mice
#17
Olga C Jorge-Torres, Karolina Szczesna, Laura Roa, Carme Casal, Louisa Gonzalez-Somermeyer, Marta Soler, Cecilia D Velasco, Pablo Martínez-San Segundo, Paolo Petazzi, Mauricio A Sáez, Raúl Delgado-Morales, Stephane Fourcade, Aurora Pujol, Dori Huertas, Artur Llobet, Sonia Guil, Manel Esteller
Rett syndrome (RTT) is the second leading cause of mental impairment in girls and is currently untreatable. RTT is caused, in more than 95% of cases, by loss-of-function mutations in the methyl CpG-binding protein 2 gene (MeCP2). We propose here a molecular target involved in RTT: the glycogen synthase kinase-3b (Gsk3b) pathway. Gsk3b activity is deregulated in Mecp2-knockout (KO) mice models, and SB216763, a specific inhibitor, is able to alleviate the clinical symptoms with consequences at the molecular and cellular levels...
May 8, 2018: Cell Reports
https://www.readbyqxmd.com/read/29742391/loss-of-mecp2-leads-to-activation-of-p53-and-neuronal-senescence
#18
Minori Ohashi, Elena Korsakova, Denise Allen, Peiyee Lee, Kai Fu, Benni S Vargas, Jessica Cinkornpumin, Carlos Salas, Jenny C Park, Igal Germanguz, Justin Langerman, Contantinos Chronis, Edward Kuoy, Stephen Tran, Xinshu Xiao, Matteo Pellegrini, Kathrin Plath, William E Lowry
To determine the role for mutations of MECP2 in Rett syndrome, we generated isogenic lines of human induced pluripotent stem cells, neural progenitor cells, and neurons from patient fibroblasts with and without MECP2 expression in an attempt to recapitulate disease phenotypes in vitro. Molecular profiling uncovered neuronal-specific gene expression changes, including induction of a senescence-associated secretory phenotype (SASP) program. Patient-derived neurons made without MECP2 showed signs of stress, including induction of P53, and senescence...
May 8, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29740174/rett-syndrome-insights-into-genetic-molecular-and-circuit-mechanisms
#19
REVIEW
Jacque P K Ip, Nikolaos Mellios, Mriganka Sur
Rett syndrome (RTT) is a severe neurological disorder caused by mutations in the gene encoding methyl-CpG-binding protein 2 (MeCP2). Almost two decades of research into RTT have greatly advanced our understanding of the function and regulation of the multifunctional protein MeCP2. Here, we review recent advances in understanding how loss of MeCP2 impacts different stages of brain development, discuss recent findings demonstrating the molecular role of MeCP2 as a transcriptional repressor, assess primary and secondary effects of MeCP2 loss and examine how loss of MeCP2 can result in an imbalance of neuronal excitation and inhibition at the circuit level along with dysregulation of activity-dependent mechanisms...
May 8, 2018: Nature Reviews. Neuroscience
https://www.readbyqxmd.com/read/29739797/epigenetic-regulation-of-aldosterone-synthase-gene-by-sodium-and-angiotensin-ii
#20
Yoshimichi Takeda, Masashi Demura, Fen Wang, Shigehiro Karashima, Takashi Yoneda, Mitsuhiro Kometani, Atsushi Hashimoto, Daisuke Aono, Shin-Ichi Horike, Makiko Meguro-Horike, Masakazu Yamagishi, Yoshiyu Takeda
BACKGROUND: DNA methylation is believed to be maintained in adult somatic cells. Recent findings, however, suggest that all methylation patterns are not stable. We demonstrate that stimulatory signals can change the DNA methylation status around transcription factor binding sites and a transcription start site and activate expression of the aldosterone synthase gene ( CYP11B2 ). METHODS AND RESULTS: DNA methylation of CYP11B2 was analyzed in aldosterone-producing adenomas, nonfunctioning adrenal adenomas, and adrenal glands and compared with the gene expression levels...
May 8, 2018: Journal of the American Heart Association
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