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neuronal epigenetics

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https://www.readbyqxmd.com/read/28634230/similarity-in-gene-regulatory-networks-suggests-that-cancer-cells-share-characteristics-of-embryonic-neural-cells
#1
Zan Zhang, Anhua Lei, Liyang Xu, Lu Chen, Yonglong Chen, Xuena Zhang, Yan Gao, Xiaoli Yang, Min Zhang, Ying Cao
Cancer cells are immature cells resulting from cellular reprogramming by gene misregulation, and re-differentiation is expected to reduce malignancy. It is unclear, however, whether cancer cells can undergo terminal differentiation. Here, we show that, inhibition of the epigenetic modification enzymes enhancer of zeste homolog 2 (EZH2), histone deacetylases (HDACs) 1 and 3, lysine demethylase 1A (LSD1), or DNA methyltransferase 1 (DNMT1), which all promote cancer development and progression, leads to postmitotic neuron-like differentiation with loss of malignant features in distinct solid cancer cell lines...
June 20, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28628196/molecular-mechanisms-of-experience-dependent-maturation-in-cortical-gabaergic-inhibition
#2
REVIEW
M Ridzwana Begum, Judy C G Sng
Critical periods (CP) in early postnatal life are periods of plasticity during which the neuronal circuitry is most receptive to environmental stimuli. These early experiences translate to a more permanent and sophisticated neuronal connection in the adult brain systems. Multiple studies have pointed to the development of inhibitory circuitry as one of the central factors for the onset of critical periods. We discuss several molecular mechanisms regulating inhibitory circuit maturation and CP, from gene transcription level to protein signaling level...
June 19, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28620760/notch-an-interactive-player-in-neurogenesis-and-disease
#3
REVIEW
Runrui Zhang, Anna Engler, Verdon Taylor
Notch signaling is evolutionarily conserved from Drosophila to human. It plays critical roles in neural stem cell maintenance and neurogenesis in the embryonic brain as well as in the adult brain. Notch functions greatly depend on careful regulation and cross-talk with other regulatory mechanisms. Deregulation of Notch signaling is involved in many neurodegenerative diseases and brain disorders. Here, we summarize the fundamental role of Notch in neuronal development and specification and discuss how epigenetic regulation and pathway cross-talk contribute to Notch function...
June 15, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28608855/mice-lacking-the-chromodomain-helicase-dna-binding-5-chromatin-remodeler-display-autism-like-characteristics
#4
M T Pisansky, A E Young, M B O'Connor, I I Gottesman, A Bagchi, J C Gewirtz
Although autism spectrum disorders (ASDs) share a core set of nosological features, they exhibit substantial genetic heterogeneity. A parsimonious hypothesis posits that dysregulated epigenetic mechanisms represent common pathways in the etiology of ASDs. To investigate this hypothesis, we generated a novel mouse model resulting from brain-specific deletion of chromodomain helicase DNA-binding 5 (Chd5), a chromatin remodeling protein known to regulate neuronal differentiation and a member of a gene family strongly implicated in ASDs...
June 13, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28607401/novel-class-iia-selective-histone-deacetylase-inhibitors-discovered-using-an-in-silico-virtual-screening-approach
#5
Kai-Cheng Hsu, Chang-Yi Liu, Tony Eight Lin, Jui-Hua Hsieh, Tzu-Ying Sung, Hui-Ju Tseng, Jinn-Moon Yang, Wei-Jan Huang
Histone deacetylases (HDAC) contain eighteen isoforms that can be divided into four classes. Of these isoform enzymes, class IIa (containing HDAC4, 5, 7 and 9) target unique substrates, some of which are client proteins associated with epigenetic control. Class IIa HDACs are reportedly associated with some neuronal disorders, making HDACs therapeutic targets for treating neurodegenerative diseases. Additionally, some reported HDAC inhibitors contain hydroxamate moiety that chelates with zinc ion to become the cofactor of HDAC enzymes...
June 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28607150/wnt3a-induces-the-expression-of-acetylcholinesterase-during-osteoblast-differentiation-via-the-runx2-transcription-factor
#6
Miranda L Xu, Cathy W C Bi, Etta Y L Liu, Tina T X Dong, Karl W K Tsim
Acetylcholinesterase (AChE) hydrolyzes acetylcholine to terminate cholinergic transmission in neurons. Apart from this AChE activity, emerging evidence suggests that AChE could also function in other, nonneuronal cells. For instance, in bone, AChE exists as a proline-rich membrane anchor (PRiMA)-linked globular form in osteoblasts, in which it is proposed to play a noncholinergic role in differentiation. However, this hypothesis is untested. Here, we found that in cultured rat osteoblasts, AChE expression was increased in parallel with osteoblastic differentiation...
June 12, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28606110/a-c9orf72-bac-mouse-model-recapitulates-key-epigenetic-perturbations-of-als-ftd
#7
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
#8
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/28599306/panobinostat-a-histone-deacetylase-inhibitor-suppresses-leptomeningeal-seeding-in-a-medulloblastoma-animal-model
#9
Ji Hoon Phi, Seung Ah Choi, Pil Ae Kwak, Ji Yeoun Lee, Kyu-Chang Wang, Do Won Hwang, Seung-Ki Kim
Leptomeningeal seeding is a strong negative prognostic factor for medulloblastoma (MB). The mechanism of leptomeningeal seeding is unclear but may involve epigenetic regulation. In this study, we evaluated the feasibility of a histone deacetylase (HDAC) inhibitor, panobinostat, in the suppression of MB leptomeningeal seeding.Panobinostat decreased the cell viability and proliferation, inducing cell cycle arrest and apoptosis in MB cell lines. The migration and adhesion capabilities were significantly decreased...
May 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28598844/combustion-derived-nanoparticles-in-key-brain-target-cells-and-organelles-in-young-urbanites-culprit-hidden-in-plain-sight-in-alzheimer-s-disease-development
#10
Angélica González-Maciel, Rafael Reynoso-Robles, Ricardo Torres-Jardón, Partha S Mukherjee, Lilian Calderón-Garcidueñas
Millions of children and young adults are exposed to fine particulate matter (PM2.5) and ozone, associated with Alzheimer's disease (AD) risk. Mexico City (MC) children exhibit systemic and brain inflammation, low cerebrospinal fluid (CSF) Aβ1-42, breakdown of nasal, olfactory, alveolar-capillary, duodenal, and blood-brain barriers, volumetric and metabolic brain changes, attention and short-term memory deficits, and hallmarks of AD and Parkinson's disease. Airborne iron-rich strongly magnetic combustion-derived nanoparticles (CDNPs) are present in young urbanites' brains...
June 3, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28597915/dissecting-lsd1-dependent-neuronal-maturation-in-the-olfactory-epithelium
#11
Julie H Coleman, Brian Lin, James E Schwob
Neurons in the olfactory epithelium (OE) each express a single dominant olfactory receptor (OR) allele from among roughly 1000 different OR genes. While monogenic and monoallelic OR expression has been appreciated for over two decades, regulators of this process are still being described; most recently, epigenetic modifiers have been of high interest as silent OR genes are decorated with transcriptionally-repressive trimethylated histone 3 lysine 9 (H3K9me3) whereas active OR genes are decorated with transcriptionally-activating trimethylated histone 3 lysine 4 (H3K4me3)...
June 9, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/28595952/trans-resveratrol-enriched-maternal-diet-protects-the-immature-hippocampus-from-perinatal-asphyxia-in-rats
#12
Sebastian Isac, Anca Maria Panaitescu, Ana Spataru, Mara Iesanu, Alexandra Totan, Amalia Udriste, Natalia Cucu, Gheorghe Peltecu, Leon Zagrean, Ana-Maria Zagrean
Trans-resveratrol (tRESV), a polyphenol with antioxidant properties, is common in many food sources, hence easily accessible for study as a maternal dietary supplement in perinatal asphyxia (PA). Hypoxic-ischemic encephalopathy secondary to PA affects especially vulnerable brain areas such as hippocampus and is a leading cause of neonatal morbidity. The purpose of this study is to identify new epigenetic mechanisms of brain inflammation and injury related to PA and to explore the benefit of tRESV enriched maternal diet...
June 6, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28593442/remodeling-of-heterochromatin-structure-slows-neuropathological-progression-and-prolongs-survival-in-an-animal-model-of-huntington-s-disease
#13
Junghee Lee, Yu Jin Hwang, Yunha Kim, Min Young Lee, Seung Jae Hyeon, Soojin Lee, Dong Hyun Kim, Sung Jae Jang, Hyoenjoo Im, Sun-Joon Min, Hyunah Choo, Ae Nim Pae, Dong Jin Kim, Kyung Sang Cho, Neil W Kowall, Hoon Ryu
Huntington's disease (HD) is an autosomal-dominant inherited neurological disorder caused by expanded CAG repeats in exon 1 of the Huntingtin (HTT) gene. Altered histone modifications and epigenetic mechanisms are closely associated with HD suggesting that transcriptional repression may play a pathogenic role. Epigenetic compounds have significant therapeutic effects in cellular and animal models of HD, but they have not been successful in clinical trials. Herein, we report that dSETDB1/ESET, a histone methyltransferase (HMT), is a mediator of mutant HTT-induced degeneration in a fly HD model...
June 7, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28592694/opening-a-new-time-window-for-treatment-of-stroke-by-targeting-hdac2
#14
Yu-Hui Lin, Jian Dong, Ying Tang, Huan-Yu Ni, Yu Zhang, Ping Su, Hai-Ying Liang, Meng-Cheng Yao, Hong-Jin Yuan, Dong-Liang Wang, Lei Chang, Hai-Yin Wu, Chun-Xia Luo, Dong-Ya Zhu
Narrow therapeutic window limits treatments with thrombolysis and neuroprotection for most stroke patients. Widening therapeutic window remains a critical challenge. Understanding the key mechanisms underlying the pathophysiological events in the peri-infarct area where secondary injury coexists with neuroplasticity over days to weeks may offer an opportunity for expanding the therapeutic window. Here we show that ischemia-induced HDAC2 up-regulation from 5 to 7 days after stroke plays a crucial role. In this window phase, suppressing HDAC2 in the peri-infarct cortex of rodents by HDAC inhibitors, knockdown or knockout of HDAC2 promoted recovery of motor function from stroke via epigenetically enhancing cells survival and neuroplasticity of surviving neurons as well as reducing neuroinflammation, whereas over-expressing HDAC2 worsened stroke-induced functional impairment of both WT and HDAC2 CKO mice...
June 7, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28591654/hypoxia-epigenetically-confers-astrocytic-differentiation-potential-on-human-pluripotent-cell-derived-neural-precursor-cells
#15
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/28591617/neuronal-activity-regulated-alternative-mrna-splicing
#16
Guido Hermey, Nils Blüthgen, Dietmar Kuhl
Activity-regulated gene transcription underlies plasticity-dependent changes in the molecular composition and structure of neurons. Numerous genes whose expression is induced by different neuronal plasticity inducing pathways have been identified, but the alteration of gene expression levels represents only part of the complexity of the activity-regulated transcriptional program. Alternative splicing of precursor mRNA is an additional mechanism that modulates the activity-dependent transcriptional signature...
June 4, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28591566/regulation-of-clustered-protocadherin-genes-in-individual-neurons
#17
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/28588451/neurogenic-to-gliogenic-fate-transition-perturbed-by-loss-of-hmgb2
#18
Robert Bronstein, Jackson Kyle, Ariel B Abraham, Stella E Tsirka
Mouse cortical development relies heavily on a delicate balance between neurogenesis and gliogenesis. The lateral ventricular zone produces different classes of excitatory pyramidal cells until just before birth, when the production of astroglia begins to prevail. Epigenetic control of this fate shift is of critical importance and chromatin regulatory elements driving neuronal or astroglial development play an vital role. Different classes of chromatin binding proteins orchestrate the transcriptional repression of neuronal-specific genes, while allowing for the activation of astrocyte-specific genes...
2017: Frontiers in Molecular Neuroscience
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/28583088/uncovering-the-transcriptomic-and-epigenomic-landscape-of-nicotinic-receptor-genes-in-non-neuronal-tissues
#20
Bo Zhang, Pamela Madden, Junchen Gu, Xiaoyun Xing, Savita Sankar, Jennifer Flynn, Kristen Kroll, Ting Wang
BACKGROUND: Nicotinic acetylcholine receptors (nAChRs) play an important role in cellular physiology and human nicotine dependence, and are closely associated with many human diseases including cancer. For example, previous studies suggest that nAChRs can re-wire gene regulatory networks in lung cancer cell lines. However, the tissue specificity of nAChRs genes and their regulation remain unexplored. RESULT: In this study, we integrated data from multiple large genomic consortiums, including ENCODE, Roadmap Epigenomics, GTEx, and FANTOM, to define the transcriptomic and epigenomic landscape of all nicotinic receptor genes across many different human tissues and cell types...
June 5, 2017: BMC Genomics
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