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https://www.readbyqxmd.com/read/28712951/ra-induced-transcriptional-silencing-of-checkpoint-kinase-2-through-promoter-methylation-by-dnmt3b-is-required-for-neuronal-differentiation-of-p19-cells
#1
Muhammad Abid Sheikh, Yousra Saeed Malik, Xiaojuan Zhu
In a previous study, we identified several novel targets of Dnmt3b using a chromatin library from RA treated P19 cells. The present study describes the regulation of expression and function of Chk2 which was one of the target genes of Dnmt3b. ChIP followed by quantitative PCR analysis showed that recruitment of Dnmt3b on Chk2 promoter is induced following RA treatment of P19 cells. Both BGS and COBRA analysis showed that the methylation level of Chk2 promoter is progressively increased during RA induced neuronal differentiation of P19 cells...
July 13, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28710457/methyl-cpg-binding-domain-proteins-inhibit-interspecies-courtship-and-promote-aggression-in-drosophila
#2
Tarun Gupta, Hannah R Morgan, Jonathan C Andrews, Edmond R Brewer, Sarah J Certel
Reproductive isolation and speciation are driven by the convergence of environmental and genetic variation. The integration of these variation sources is thought to occur through epigenetic marks including DNA methylation. Proteins containing a methyl-CpG-binding domain (MBD) bind methylated DNA and interpret epigenetic marks, providing a dynamic yet evolutionarily adapted cellular output. Here, we report the Drosophila MBD-containing proteins, dMBD-R2 and dMBD2/3, contribute to reproductive isolation and survival behavioral strategies...
July 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28696319/combined-epigenetic-and-differentiation-based-treatment-inhibits-neuroblastoma-tumor-growth-and-links-hif2%C3%AE-to-tumor-suppression
#3
Isabelle Westerlund, Yao Shi, Konstantinos Toskas, Stuart M Fell, Shuijie Li, Olga Surova, Erik Södersten, Per Kogner, Ulrika Nyman, Susanne Schlisio, Johan Holmberg
Neuroblastoma is a pediatric cancer characterized by variable outcomes ranging from spontaneous regression to life-threatening progression. High-risk neuroblastoma patients receive myeloablative chemotherapy with hematopoietic stem-cell transplant followed by adjuvant retinoid differentiation treatment. However, the overall survival remains low; hence, there is an urgent need for alternative therapeutic approaches. One feature of high-risk neuroblastoma is the high level of DNA methylation of putative tumor suppressors...
July 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28694114/epigenetic-dysregulation-of-protocadherins-in-human-disease
#4
REVIEW
Nady El Hajj, Marcus Dittrich, Thomas Haaf
Protocadherins (Pcdhs) are a group of cell-cell adhesion molecules that are highly expressed in the nervous system and have a major function in dendrite development and neural circuit formation. However, the role protocadherins play in human health and disease remains unclear. Several recent studies have associated epigenetic dysregulation of protocadherins with possible implications for disease pathogenesis. In this review, we briefly recap the various epigenetic mechanisms regulating protocadherin genes, particularly the clustered Pcdhs...
July 7, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28691768/microbiome-inflammation-epigenetic-alterations-and-mental-diseases
#5
REVIEW
Reza Alam, Hamid M Abdolmaleky, Jin-Rong Zhou
Major mental diseases such as autism, bipolar disorder, schizophrenia, and major depressive disorder are debilitating illnesses with complex etiologies. Recent findings show that the onset and development of these illnesses cannot be well described by the one-gene; one-disease approach. Instead, their clinical presentation is thought to result from the regulative interplay of a large number of genes. Even though the involvement of many genes are likely, up regulating and activation or down regulation and silencing of these genes by the environmental factors play a crucial role in contributing to their pathogenesis...
July 10, 2017: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
https://www.readbyqxmd.com/read/28688903/differential-effects-between-developmental-and-postpubertal-exposure-to-n-methyl-n-nitrosourea-on-progenitor-cell-proliferation-of-rat-hippocampal-neurogenesis-in-relation-to-cox2-expression-in-granule-cells
#6
Yousuke Watanabe, Kota Nakajima, Sayaka Mizukami, Yumi Akahori, Nobuya Imatanaka, Gye-Hyeong Woo, Toshinori Yoshida, Makoto Shibutani
This study was performed to compare the exposure effects of N-methyl-N-nitrosourea (MNU), a cytocidal agent of proliferating cells, on rat hippocampal neurogenesis between developmental and postpubertal periods. Developmental exposure through maternal drinking water from gestational day 6 to day 21 after delivery on weaning decreased GFAP-immunoreactive ((+)) stem cells and increased immunoreactive cells indicative of subsequent progenitor and postmitotic immature neuronal populations, TUNEL(+) or p21(Cip1/Waf1+) stem/progenitor cells and COX2(+) granule cells, on postnatal day (PND) 21...
July 5, 2017: Toxicology
https://www.readbyqxmd.com/read/28685937/neuroimmunomodulatory-properties-of-dpscs-in-an-in-vitro-model-of-parkinson-s-disease
#7
Nareshwaran Gnanasegaran, Vijayendran Govindasamy, Vasudevan Mani, Noor Hayaty Abu Kasim
In neurodegenerative diseases, such as Alzheimer's and Parkinson's, microglial cell activation is thought to contribute to their degeneration by producing neurotoxic compounds. While dental pulp stem cells (DPSCs) have been regarded as the next possible cell source for cell replacement therapy (CRT), their actual role when exposed in such harsh environment remains elusive. In this study, the immunomodulatory behavior of DPSCs from human subjects was investigated in a coculture system consisting of neuron and microglia which were treated with 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine, which mimics the inflammatory conditions and contribute to degeneration of dopaminergic (DA-ergic) neurons...
July 6, 2017: IUBMB Life
https://www.readbyqxmd.com/read/28682229/-epigenetic-mechanisms-and-alcohol-use-disorders-a-potential-therapeutic-target
#8
Rémi Legastelois, Jérôme Jeanblanc, Catherine Vilpoux, Erika Bourguet, Mickael Naassila
Alcohol use disorder is a devastating illness with a profound health impact, and its development is dependent on both genetic and environmental factors. This disease occurs over time and requires changes in brain gene expression. There is converging evidence suggesting that the epigenetic processes may play a role in the alcohol-induced gene regulations and behavior such as the intervention of DNA methylation and histone acetylation. Histone acetylation, like histone methylation, is a highly dynamic process regulated by two classes of enzymes: histone acetyltransferases and histone deacetylases (HDACs)...
2017: Biologie Aujourd'hui
https://www.readbyqxmd.com/read/28671923/lncrnas-dna-methylation-and-the-pathobiology-of-exfoliation-glaucoma
#9
William M Johnson, Laura K Finnegan, Michael A Hauser, W Daniel Stamer
Exfoliation glaucoma (XFG) is a clinically aggressive and genetically distinct form of glaucoma that results in neuronal death and irreversible blindness. Gene variants associate with many neurodegenerative diseases including XFG, Parkinson's disease (PD) and Alzheimer's disease (AD). Intriguingly, variants found within the same gene can either confer risk for or provide protection against all 3 of these diseases, complicating the genetic component of pathology. Unfortunately, studies that examine proteins encoded by genes having relevant variants have failed to produce therapeutic interventions that slow or stop the progression of XFG, PD, or AD in patients...
June 30, 2017: Journal of Glaucoma
https://www.readbyqxmd.com/read/28671722/restoring-eeaqualibrium-rebalancing-excitation-and-inhibition-in-rett-mouse-model-neurons-with-early-endosome-antigen-1
#10
Kerry R Delaney
Rett syndrome is a neurological disorder resulting from loss of function of MECP2, an X-linked transcription factor, which controls expression of hundreds of genes involved in synapse formation and development by binding primarily to methylated DNA. This article is protected by copyright. All rights reserved.
July 3, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28631231/2-3-dideoxycytidine-protects-dopaminergic-neurons-in-a-mouse-model-of-parkinson-s-disease
#11
Jianyi Niu, Jing Xiong, Dan Hu, Fei Zeng, Shuke Nie, Shanping Mao, Tao Wang, Zhentao Zhang, Zhaohui Zhang
DNA polymerase-β (DNA pol-β) plays a crucial role in the pathogenesis of Parkinson's disease (PD). The aim of this study was to investigate the neuroprotective effects of a DNA polymerase-β inhibitor 2',3'-dideoxycytidine (DDC) in PD models. In the in vitro studies, primary cultured neurons were challenged with 1-methyl-4-phenylpyridinium ion (MPP(+)). The expression of DNA pol-β was assessed using western blot. The neuroprotective effect of DNA pol-β knockdown and DNA pol-β inhibitor DDC was determined using cell viability assay and caspase-3 activity assay...
June 19, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28616777/differential-regulation-of-mecp2-phosphorylation-by-laminin-in-oligodendrocytes
#12
Zalak S Parikh, Ashutosh Tripathi, Prakash P Pillai
Oligodendrocytes (OLGs) are the myelinating cells of the central nervous system (CNS), and its proper differentiation is crucial for normal functioning of neurons. Methyl-CpG-binding protein 2 (MeCP2) is a multifunctional methylated DNA binding protein; mutation of which causes Rett syndrome, a severe neurodevelopmental disorder. Previously, we reported that MeCP2 is expressed in all the stages of oligodendrocyte development, and also shown the role of MeCP2 as a transcription regulator of myelin genes in OLGs...
June 14, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28606110/a-c9orf72-bac-mouse-model-recapitulates-key-epigenetic-perturbations-of-als-ftd
#13
Rustam Esanov, Gabriela Toro Cabrera, Nadja S Andrade, Tania F Gendron, Robert H Brown, Michael Benatar, Claes Wahlestedt, Christian Mueller, Zane Zeier
BACKGROUND: Amyotrophic Lateral Sclerosis (ALS) is a fatal and progressive neurodegenerative disorder with identified genetic causes representing a significant minority of all cases. A GGGGCC hexanucleotide repeat expansion (HRE) mutation within the C9ORF72 gene has recently been identified as the most frequent known cause of ALS. The expansion leads to partial heterochromatinization of the locus, yet mutant RNAs and dipeptide repeat proteins (DPRs) are still produced in sufficient quantities to confer neurotoxicity...
June 12, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28605464/strand-specific-cpg-hemimethylation-a-novel-epigenetic-modification-functional-for-genomic-imprinting
#14
Iris Patiño-Parrado, Álvaro Gómez-Jiménez, Noelia López-Sánchez, José M Frade
Imprinted genes are regulated by allele-specific differentially DNA-methylated regions (DMRs). Epigenetic methylation of the CpGs constituting these DMRs is established in the germline, resulting in a 5-methylcytosine-specific pattern that is tightly maintained in somatic tissues. Here, we show a novel epigenetic mark, characterized by strand-specific hemimethylation of contiguous CpG sites affecting the germline DMR of the murine Peg3, but not Snrpn, imprinted domain. This modification is enriched in tetraploid cortical neurons, a cell type where evidence for a small proportion of formylmethylated CpG sites within the Peg3-controlling DMR is also provided...
June 9, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28603210/emerging-mechanisms-underlying-astrogenesis-in-the-developing-mammalian-brain
#15
REVIEW
Jun Takouda, Sayako Katada, Kinichi Nakashima
In the developing brain, the three major cell types, i.e., neurons, astrocytes and oligodendrocytes, are generated from common multipotent neural stem cells (NSCs). In particular, astrocytes eventually occupy a great fraction of the brain and play pivotal roles in the brain development and functions. However, NSCs cannot produce the three major cell types simultaneously from the beginning; e.g., it is known that neurogenesis precedes astrogenesis during brain development. How is this fate switching achieved? Many studies have revealed that extracellular cues and intracellular programs are involved in the transition of NSC fate specification...
2017: Proceedings of the Japan Academy. Series B, Physical and Biological Sciences
https://www.readbyqxmd.com/read/28597690/dna-methylation-and-copy-number-variation-analyses-of-human-embryonic-stem-cell-derived-neuroprogenitors-after-low-dose-decabromodiphenyl-ether-and-or-bisphenol-a-exposure
#16
L Du, W Sun, X M Li, X Y Li, W Liu, D Chen
The polybrominated diphenyl ether flame retardants decabromodiphenyl ether (BDE-209) and bisphenol A (BPA) are environmental contaminants that can cross the placenta and exert toxicity in the developing fetal nervous system. Copy number variants (CNVs) play a role in a number of genetic disorders and may be implicated in BDE-209/BPA teratogenicity. In this study, we found that BDE-209 and/or BPA exposure decreased neural differentiation efficiency of human embryonic stem cells (hESCs), although there was a >90% induction of neuronal progenitor cells (NPCs) from exposed hESCs...
January 1, 2017: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/28591654/hypoxia-epigenetically-confers-astrocytic-differentiation-potential-on-human-pluripotent-cell-derived-neural-precursor-cells
#17
Tetsuro Yasui, Naohiro Uezono, Hideyuki Nakashima, Hirofumi Noguchi, Taito Matsuda, Tomoko Noda-Andoh, Hideyuki Okano, Kinichi Nakashima
Human neural precursor cells (hNPCs) derived from pluripotent stem cells display a high propensity for neuronal differentiation, but they require long-term culturing to differentiate efficiently into astrocytes. The mechanisms underlying this biased fate specification of hNPCs remain elusive. Here, we show that hypoxia confers astrocytic differentiation potential on hNPCs through epigenetic gene regulation, and that this was achieved by cooperation between hypoxia-inducible factor 1α and Notch signaling, accompanied by a reduction of DNA methylation level in the promoter region of a typical astrocyte-specific gene, Glial fibrillary acidic protein...
June 6, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28591566/regulation-of-clustered-protocadherin-genes-in-individual-neurons
#18
REVIEW
Teruyoshi Hirayama, Takeshi Yagi
Individual neurons are basic functional units in the complex system of the brain. One aspect of neuronal individuality is generated by stochastic and combinatorial expression of diverse clustered protocadherins (Pcdhs), encoded by the Pcdha, Pcdhb, and Pcdhg gene clusters, that are critical for several aspects of neural circuit formation. Each clustered Pcdh gene has its own promoter containing conserved sequences and is transcribed by a promoter choice mechanism involving interaction between the promoter and enhancers...
June 4, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28585265/past-present-and-future-of-epigenetics-in-brain-sexual-differentiation
#19
REVIEW
Nancy G Forger
Sexual differentiation has long been considered "epigenetic," although the meaning of that word has shifted over time. Here we track the evolution of ideas about epigenetics in sexual differentiation, and identify principles that have emerged from recent studies. Experiments manipulating a particular epigenetic mechanism during neonatal life demonstrate a role for both histone acetylation and DNA methylation in the development of sex differences in the brain and behavior of rodents. In addition, hormone-dependent sex differences in the number of neurons of a particular phenotype may be programmed by differences in DNA methylation early in life...
June 6, 2017: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/28577753/cocaine-induced-chromatin-modifications-associate-with-increased-expression-and-three-dimensional-looping-of-auts2
#20
Olivia Engmann, Benoit Labonté, Amanda Mitchell, Pavel Bashtrykov, Erin S Calipari, Chaggai Rosenbluh, Yong-Hwee E Loh, Deena M Walker, Dominika Burek, Peter J Hamilton, Orna Issler, Rachael L Neve, Gustavo Turecki, Yasmin Hurd, Andrew Chess, Li Shen, Isabelle Mansuy, Albert Jeltsch, Schahram Akbarian, Eric J Nestler
BACKGROUND: Exposure to drugs of abuse alters the epigenetic landscape of the brain's reward regions, such as the nucleus accumbens. We investigated how combinations of chromatin modifications affect genes that regulate responses to cocaine. We focused on Auts2, a gene linked to human evolution and cognitive disorders, which displays strong clustering of cocaine-induced chromatin modifications in this brain region. METHODS: We combined chromosome conformation capture, circularized chromosome conformation capture, and related approaches with behavioral paradigms relevant to cocaine phenotypes...
May 5, 2017: Biological Psychiatry
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