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Epigenetic modification

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https://www.readbyqxmd.com/read/28346453/activity-induced-histone-modifications-govern-neurexin-1-mrna-splicing-and-memory-preservation
#1
Xinlu Ding, Sanxiong Liu, Miaomiao Tian, Wenhao Zhang, Tao Zhu, Dongdong Li, Jiawei Wu, HaiTeng Deng, Yichang Jia, Wei Xie, Hong Xie, Ji-Song Guan
Epigenetic mechanisms regulate the formation, consolidation and reconsolidation of memories. However, the signaling path from neuronal activation to epigenetic modifications within the memory-related brain circuit remains unknown. We report that learning induces long-lasting histone modifications in hippocampal memory-activated neurons to regulate memory stability. Neuronal activity triggers a late-onset shift in Nrxn1 splice isoform choice at splicing site 4 by accumulating a repressive histone marker, H3K9me3, to modulate the splicing process...
March 27, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28346445/potential-energy-landscapes-identify-the-information-theoretic-nature-of-the-epigenome
#2
Garrett Jenkinson, Elisabet Pujadas, John Goutsias, Andrew P Feinberg
Epigenetics is the study of biochemical modifications carrying information independent of DNA sequence, which are heritable through cell division. In 1940, Waddington coined the term "epigenetic landscape" as a metaphor for pluripotency and differentiation, but methylation landscapes have not yet been rigorously computed. Using principles from statistical physics and information theory, we derive epigenetic energy landscapes from whole-genome bisulfite sequencing (WGBS) data that enable us to quantify methylation stochasticity genome-wide using Shannon's entropy, associating it with chromatin structure...
March 27, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28346436/detailed-comparison-of-retroviral-vectors-and-promoter-configurations-for-stable-and-high-transgene-expression-in-human-induced-pluripotent-stem-cells
#3
D Hoffmann, J W Schott, F K Geis, L Lange, F-J Müller, D Lenz, D Zychlinski, D Steinemann, M Morgan, T Moritz, A Schambach
Correction of patient-specific induced pluripotent stem cells (iPSC) upon gene delivery through retroviral vectors offers new treatment perspectives for monogenetic diseases. Gene-modified iPSC clones can be screened for safe integration sites and differentiated into transplantable cells of interest. However, the current bottleneck is epigenetic vector silencing. In order to identify the most suitable retroviral expression system in iPSC, we systematically compared vectors from different retroviral genera, different promoters and their combination with ubiquitous chromatin opening elements (UCOE), and several envelope pseudotypes...
March 27, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28346403/near-infrared-optogenetic-pair-for-protein-regulation-and-spectral-multiplexing
#4
Taras A Redchuk, Evgeniya S Omelina, Konstantin G Chernov, Vladislav V Verkhusha
Multifunctional optogenetic systems are in high demand for use in basic and biomedical research. Near-infrared-light-inducible binding of bacterial phytochrome BphP1 to its natural PpsR2 partner is beneficial for simultaneous use with blue-light-activatable tools. However, applications of the BphP1-PpsR2 pair are limited by the large size, multidomain structure and oligomeric behavior of PpsR2. Here, we engineered a single-domain BphP1 binding partner, Q-PAS1, which is three-fold smaller and lacks oligomerization...
March 27, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28345651/epigenome-mapping-highlights-chromatin-mediated-gene-regulation-in-the-protozoan-parasite-trichomonas-vaginalis
#5
Min-Ji Song, Mikyoung Kim, Yeeun Choi, Myung-Hee Yi, Juri Kim, Soon-Jung Park, Tai-Soon Yong, Hyoung-Pyo Kim
Trichomonas vaginalis is an extracellular flagellated protozoan parasite that causes trichomoniasis, one of the most common non-viral sexually transmitted diseases. To survive and to maintain infection, T. vaginalis adapts to a hostile host environment by regulating gene expression. However, the mechanisms of transcriptional regulation are poorly understood for this parasite. Histone modification has a marked effect on chromatin structure and directs the recruitment of transcriptional machinery, thereby regulating essential cellular processes...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28345525/tolerance-of-monocytes-and-macrophages-in-response-to-bacterial-endotoxin
#6
Ewelina Wiśnik, Ewa Pikus, Piotr Duchnowicz, Maria Koter-Michalak
Monocytes belong to myeloid effector cells, which constitute the first line of defense against pathogens, also called the nonspecific immune system and play an important role in the maintenance of tissue homeostasis. In response to stimulation, monocytes differentiate into macrophages capable of microorganism phagocytosis and secrete factors that play a key role in the regulation of immune responses. However excessive exposure of monocytes/macrophages to the lipopolysaccharide (LPS) of Gram negative bacteria leads to the acquisition of immune tolerance by these cells...
March 7, 2017: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/28344923/impact-of-drug-treatment-at-neonatal-ages-on-variability-of-drug-metabolism-and-drug-drug-interactions-in-adult-life
#7
Stephanie Piekos, Chad Pope, Austin Ferrara, Xiao-Bo Zhong
PURPOSE OF REVIEW: As the number of patients taking more than one medication concurrently continues to increase, predicting and preventing drug-drug interactions (DDIs) is now more important than ever. Administration of one drug can cause changes in the expression and activity of drug metabolizing enzymes (DMEs) and alter the efficacy or toxicity of other medications that are substrates for these enzymes, resulting in a DDI. In today's medical practice, potential DDIs are evaluated based on the current medications a patient is taking with little regard to drugs the patient has been exposed to in the past...
February 2017: Current Pharmacology Reports
https://www.readbyqxmd.com/read/28343968/met-2-dependent-h3k9-methylation-suppresses-transgenerational-small-rna-inheritance
#8
Itamar Lev, Uri Seroussi, Hila Gingold, Roberta Bril, Sarit Anava, Oded Rechavi
In C. elegans, alterations to chromatin produce transgenerational effects, such as inherited increase in lifespan and gradual loss of fertility. Inheritance of histone modifications can be induced by double-stranded RNA-derived heritable small RNAs. Here, we show that the mortal germline phenotype, which is typical of met-2 mutants, defective in H3K9 methylation, depends on HRDE-1, an argonaute that carries small RNAs across generations, and is accompanied by accumulated transgenerational misexpression of heritable small RNAs...
March 21, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28343122/genetic-and-epigenetic-variation-of-transposable-elements-in-arabidopsis
#9
REVIEW
Charles J Underwood, Ian R Henderson, Robert A Martienssen
Transposable elements are mobile genetic elements that are prevalent in plant genomes and are silenced by epigenetic modification. Different epigenetic modification pathways play distinct roles in the control of transposable element transcription, replication and recombination. The Arabidopsis genome contains families of all of the major transposable element classes, which are differentially enriched in particular genomic regions. Whole genome sequencing and DNA methylation profiling of hundreds of natural Arabidopsis accessions has revealed that transposable elements exhibit significant intraspecific genetic and epigenetic variation, and that genetic variation often underlies epigenetic variation...
March 23, 2017: Current Opinion in Plant Biology
https://www.readbyqxmd.com/read/28342734/integration-of-microbiome-and-epigenome-to-decipher-the-pathogenesis-of-autoimmune-diseases
#10
REVIEW
Beidi Chen, Luxi Sun, Xuan Zhang
The interaction between genetic predisposition and environmental factors are of great significance in the pathogenesis and development of autoimmune diseases (AIDs). The human mucosa is the most frequent site that interacts with the exterior environment, and commensal microbiota at the gut and other human mucosal cavities play a crucial role in the regulation of immune system. Growing evidence has shown that the compositional and functional changes of mucosal microbiota are closely related to AIDs. Gut dysbiosis not only influence the expression level of Toll-like receptors (TLRs) of antigen presenting cells, but also contribute to Th17/Treg imbalance...
March 22, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28342717/slow-chromatin-dynamics-allow-polycomb-target-genes-to-filter-fluctuations-in-transcription-factor-activity
#11
Scott Berry, Caroline Dean, Martin Howard
Genes targeted by Polycomb repressive complex 2 (PRC2) are regulated in cis by chromatin modifications and also in trans by diffusible regulators such as transcription factors. Here, we introduce a mathematical model in which transcription directly antagonizes Polycomb silencing, thereby linking these cis- and trans-regulatory inputs to gene expression. The model is parameterized by recent experimental data showing that PRC2-mediated repressive chromatin modifications accumulate extremely slowly. The model generates self-perpetuating, bistable active and repressed chromatin states that persist through DNA replication, thereby ensuring high-fidelity transmission of the current chromatin state...
March 21, 2017: Cell Systems
https://www.readbyqxmd.com/read/28342553/myelin-changes-in-alexander-disease
#12
U Gómez-Pinedo, M Duran-Moreno, S Sirerol-Piquer, J Matias-Guiu
INTRODUCTION: Alexander disease (AxD) is a type of leukodystrophy. Its pathological basis, along with myelin loss, is the appearance of Rosenthal bodies, which are cytoplasmic inclusions in astrocytes. Mutations in the gene coding for GFAP have been identified as a genetic basis for AxD. However, the mechanism by which these variants produce the disease is not understood. DEVELOPMENT: The most widespread hypothesis is that AxD develops when a gain of function mutation causes an increase in GFAP...
March 22, 2017: Neurología: Publicación Oficial de la Sociedad Española de Neurología
https://www.readbyqxmd.com/read/28341870/influences-of-the-gut-microbiota-on-dna-methylation-and-histone-modification
#13
REVIEW
Jianzhong Ye, Wenrui Wu, Yating Li, Lanjuan Li
The gut microbiota is a vast ensemble of microorganisms inhabiting the mammalian gastrointestinal tract that can impact physiologic and pathologic processes. However, our understanding of the underlying mechanism for the dynamic interaction between host and gut microbiota is still in its infancy. The highly evolved epigenetic modifications allow hosts to reprogram the genome in response to environmental stimuli, which may play a key role in triggering multiple human diseases. In spite of increasing studies in gut microbiota and epigenetic modifications, the correlation between them has not been well elaborated...
March 24, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28341809/structural-basis-of-molecular-recognition-of-helical-histone-h3-tail-by-phd-finger-domains
#14
Alessio Bortoluzzi, Anastasia Amato, Xavier Lucas, Manuel Blank, Alessio Ciulli
The plant homeodomain (PHD) fingers are amongst the largest family of epigenetic domains, first characterized as readers of methylated H3K4. Readout of histone post-translational modifications by PHDs has been the subject of intense investigation, however less is known about the recognition of secondary structure features within histone tail itself. We solved the crystal structure of the PHD finger of the bromodomain adjacent to zinc finger 2A (BAZ2A, also known as TIP5) in complex with unmodified N-terminal histone H3 tail...
March 24, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28340733/migration-test-of-bisphenol-a-from-polycarbonate-cups-using-excitation-emission-fluorescence-data-with-parallel-factor-analysis
#15
M L Spagnuolo, F Marini, L A Sarabia, M C Ortiz
Bisphenol A (BPA) is one of the most largely produced chemical in the world; it is used to make plastics and epoxy resins. The endocrine disruptor potential of BPA is well known, but recent researches suggest a relationship between chronic exposure to BPA, genotoxic activity and epigenetic modifications. The main source of exposure to BPA includes food contact materials (FCM). Thus simple and robust test methods are needed to improve the migration test of BPA. In this work, a non-separative, easy, fast and inexpensive spectrofluorimetric method based on the second order calibration of excitation-emission fluorescence matrices (EEMs) was proposed for the determination of BPA...
May 15, 2017: Talanta
https://www.readbyqxmd.com/read/28340599/dna-methylation-changes-at-infertility-genes-in-newborn-twins-conceived-by-in-vitro-fertilisation
#16
Juan E Castillo-Fernandez, Yuk Jing Loke, Sebastian Bass-Stringer, Fei Gao, Yudong Xia, Honglong Wu, Hanlin Lu, Yuan Liu, Jun Wang, Tim D Spector, Richard Saffery, Jeffrey M Craig, Jordana T Bell
BACKGROUND: The association of in vitro fertilisation (IVF) and DNA methylation has been studied predominantly at regulatory regions of imprinted genes and at just thousands of the ~28 million CpG sites in the human genome. METHODS: We investigated the links between IVF and DNA methylation patterns in whole cord blood cells (n = 98) and cord blood mononuclear cells (n = 82) from newborn twins using genome-wide methylated DNA immunoprecipitation coupled with deep sequencing...
March 24, 2017: Genome Medicine
https://www.readbyqxmd.com/read/28337317/structural-requirements-of-hdac-inhibitors-saha-analogues-modified-at-the-c2-position-display-hdac6-8-selectivity
#17
Ahmed T Negmeldin, Geetha Padige, Anton V Bieliauskas, Mary Kay H Pflum
Histone deacetylase (HDAC) proteins are epigenetic regulators that deacetylate protein substrates, leading to subsequent changes in cell function. HDAC proteins are implicated in cancers, and several HDAC inhibitors have been approved by the FDA as anticancer drugs, including SAHA (suberoylanilide hydroxamic acid; Vorinostat and Zolinza). Unfortunately, SAHA inhibits most HDAC isoforms, which limits its use as a pharmacological tool and may lead to side effects in the clinic. In this work SAHA analogues substituted at the C2 position were synthesized and screened for HDAC isoform selectivity in vitro and in cells...
March 9, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28336670/pi3k-pathway-regulates-er-dependent-transcription-in-breast-cancer-through-the-epigenetic-regulator-kmt2d
#18
Eneda Toska, Hatice U Osmanbeyoglu, Pau Castel, Carmen Chan, Ronald C Hendrickson, Moshe Elkabets, Maura N Dickler, Maurizio Scaltriti, Christina S Leslie, Scott A Armstrong, José Baselga
Activating mutations in PIK3CA, the gene encoding phosphoinositide-(3)-kinase α (PI3Kα), are frequently found in estrogen receptor (ER)-positive breast cancer. PI3Kα inhibitors, now in late-stage clinical development, elicit a robust compensatory increase in ER-dependent transcription that limits therapeutic efficacy. We investigated the chromatin-based mechanisms leading to the activation of ER upon PI3Kα inhibition. We found that PI3Kα inhibition mediates an open chromatin state at the ER target loci in breast cancer models and clinical samples...
March 24, 2017: Science
https://www.readbyqxmd.com/read/28336495/genetic-variation-and-epigenetic-modification-of-the-prodynorphin-gene-in-peripheral-blood-cells-in-alcoholism
#19
Claudio D'Addario, Klementy Shchetynsky, Mariangela Pucci, Carlo Cifani, Agneta Gunnar, Vladana Vukojević, Leonid Padyukov, Lars Terenius
Dynorphins are critically involved in the development, maintenance and relapse of alcoholism. Alcohol-induced changes in the prodynorphin gene expression may be influenced by both gene polymorphisms and epigenetic modifications. The present study of human alcoholics aims to evaluate DNA methylation patterns in the prodynorphin gene (PDYN) promoter and to identify single nucleotide polymorphisms (SNPs) associated with alcohol dependence and with altered DNA methylation. Genomic DNA was isolated from peripheral blood cells of alcoholics and healthy controls, and DNA methylation was studied in the PDYN promoter by bisulfite pyrosequencing...
March 20, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28336320/preliminary-research-on-dna-methylation-changes-during-murine-palatogenesis-induced-by-tcdd
#20
Chen Wang, Xin-Gang Yuan, Cui-Ping Liu, Sha-Na Zhai, Ding-Wen Zhang, Yue-Xian Fu
2,3,7,8-Tetrachlrodibenzo-p-dioxin (TCDD) has been shown to induce cleft palate through growth factor and receptor expression changes during palatogenesis. DNA methylation is an important epigenetic modification that can regulate gene expressions and may be involved in TCDD-induced cleft palate. In this study, we investigated the effects of TCDD on the global and CpG DNA methylation status and the expression levels of DNA methyltransferases (Dnmts) in palate tissue of fetal mice. Pregnant C57BL/6J mice were administered with corn oil or TCDD 28 μg/kg at gestation day 10...
February 12, 2017: Journal of Cranio-maxillo-facial Surgery
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