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https://www.readbyqxmd.com/read/28918065/the-role-of-epigenetics-in-lysosomal-storage-disorders-uncharted-territory
#1
REVIEW
Shahzeb Hassan, Ellen Sidransky, Nahid Tayebi
The study of the contribution of epigenetic mechanisms, including DNA methylation, histone modifications, and microRNAs, to human disease has enhanced our understanding of different cellular processes and diseased states, as well as the effect of environmental factors on phenotypic outcomes. Epigenetic studies may be particularly relevant in evaluating the clinical heterogeneity observed in monogenic disorders. The lysosomal storage disorders are Mendelian disorders characterized by a wide spectrum of associated phenotypes, ranging from neonatal presentations to symptoms that develop in late adulthood...
August 1, 2017: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/28918030/lncrna-trerna1-function-as-an-enhancer-of-snai1-promotes-gastric-cancer-metastasis-by-regulating-epithelial-mesenchymal-transition
#2
Huazhang Wu, Ying Hu, Xiufang Liu, Wei Song, Pihai Gong, Kun Zhang, Zhenxing Chen, Menghan Zhou, Xiaohui Shen, Yanyan Qian, Hong Fan
Long noncoding RNA (lncRNA) has been implicated in cancer, but little is known about the role of lncRNAs as regulators of tumor metastasis. In the present study, we demonstrate that lncRNA TRERNA1 acts like an enhancer of SNAI1 to promote cell invasion and migration and to contribute to metastasis of gastric cancer (GC). TRERNA1 is significantly unregulated in GCs and GC cell lines. Increased TRERNA1 is positively correlated with lymph node metastasis of GCs. RNA immunoprecipitation (RIP) and chromatin immunoprecipitation (ChIP) assays revealed that TRERNA1 functions as a scaffold to recruit EZH2 to epigenetically silence epithelial-mesenchymal transition marker CDH1 by H3K27me3 of its promoter region...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28917501/personalized-translational-epilepsy-research-novel-approaches-and-future-perspectives-part-i-clinical-and-network-analysis-approaches
#3
REVIEW
Felix Rosenow, Natascha van Alphen, Albert Becker, Andreas Chiocchetti, Ralf Deichmann, Thomas Deller, Thomas Freiman, Christine M Freitag, Johannes Gehrig, Anke M Hermsen, Peter Jedlicka, Christian Kell, Karl Martin Klein, Susanne Knake, Dimitri M Kullmann, Stefan Liebner, Braxton A Norwood, Diana Omigie, Karlheinz Plate, Andreas Reif, Philipp S Reif, Yvonne Reiss, Jochen Roeper, Michael W Ronellenfitsch, Stephanie Schorge, Gerhard Schratt, Stephan W Schwarzacher, Joachim P Steinbach, Adam Strzelczyk, Jochen Triesch, Marlies Wagner, Matthew C Walker, Frederic von Wegner, Sebastian Bauer
Despite the availability of more than 15 new "antiepileptic drugs", the proportion of patients with pharmacoresistant epilepsy has remained constant at about 20-30%. Furthermore, no disease-modifying treatments shown to prevent the development of epilepsy following an initial precipitating brain injury or to reverse established epilepsy have been identified to date. This is likely in part due to the polyetiologic nature of epilepsy, which in turn requires personalized medicine approaches. Recent advances in imaging, pathology, genetics and epigenetics have led to new pathophysiological concepts and the identification of monogenic causes of epilepsy...
September 13, 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/28917498/personalized-translational-epilepsy-research-novel-approaches-and-future-perspectives-part-ii-experimental-and-translational-approaches
#4
REVIEW
Sebastian Bauer, Natascha van Alphen, Albert Becker, Andreas Chiocchetti, Ralf Deichmann, Thomas Deller, Thomas Freiman, Christine M Freitag, Johannes Gehrig, Anke M Hermsen, Peter Jedlicka, Christian Kell, Karl Martin Klein, Susanne Knake, Dimitri M Kullmann, Stefan Liebner, Braxton A Norwood, Diana Omigie, Karlheinz Plate, Andreas Reif, Philipp S Reif, Yvonne Reiss, Jochen Roeper, Michael W Ronellenfitsch, Stephanie Schorge, Gerhard Schratt, Stephan W Schwarzacher, Joachim P Steinbach, Adam Strzelczyk, Jochen Triesch, Marlies Wagner, Matthew C Walker, Frederic von Wegner, Felix Rosenow
Despite the availability of more than 15 new "antiepileptic drugs", the proportion of patients with pharmacoresistant epilepsy has remained constant at about 20-30%. Furthermore, no disease-modifying treatments shown to prevent the development of epilepsy following an initial precipitating brain injury or to reverse established epilepsy have been identified to date. This is likely in part due to the polyetiologic nature of epilepsy, which in turn requires personalized medicine approaches. Recent advances in imaging, pathology, genetics, and epigenetics have led to new pathophysiological concepts and the identification of monogenic causes of epilepsy...
September 13, 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/28917077/pancreatic-%C3%AE-cells-and-type-2-diabetes-development
#5
Miranda-Perez Maria Elizabeth, Alarcon-Aguilar, Francisco J, Ortega-Camarillo Clara, Escobar-Villanueva, Maria Del Carmen
Diabetes mellitus (DM) is a group of metabolic disorders characterized by hyperglycemia. In particular, type 2 diabetes (T2D) represents one of the main causes of death in the world, and those suffering from it have a lower quality of life. Although there are multiple hypotheses about the pathophysiological mechanisms that lead to the development of T2D, the effects of this pathology on pancreatic β-cells are often ignored. We now know that in addition to genetic defects, β-cell organellar dysfunction participates in the earliest stages of the disease; other factors also contribute to this dysfunction, such as excessive production of reactive oxygen species and a decrease in cellular volume and mass...
2017: Current Diabetes Reviews
https://www.readbyqxmd.com/read/28916933/interactions-between-genetics-lifestyle-and-environmental-factors-for-healthcare
#6
Yuxin Lin, Jiajia Chen, Bairong Shen
The occurrence and progression of diseases are strongly associated with a combination of genetic, lifestyle, and environmental factors. Understanding the interplay between genetic and nongenetic components provides deep insights into disease pathogenesis and promotes personalized strategies for people healthcare. Recently, the paradigm of systems medicine, which integrates biomedical data and knowledge at multidimensional levels, is considered to be an optimal way for disease management and clinical decision-making in the era of precision medicine...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28916764/rapid-and-reversible-epigenome-editing-by-endogenous-chromatin-regulators
#7
Simon M G Braun, Jacob G Kirkland, Emma J Chory, Dylan Husmann, Joseph P Calarco, Gerald R Crabtree
Understanding the causal link between epigenetic marks and gene regulation remains a central question in chromatin biology. To edit the epigenome we developed the FIRE-Cas9 system for rapid and reversible recruitment of endogenous chromatin regulators to specific genomic loci. We enhanced the dCas9-MS2 anchor for genome targeting with Fkbp/Frb dimerizing fusion proteins to allow chemical-induced proximity of a desired chromatin regulator. We find that mSWI/SNF (BAF) complex recruitment is sufficient to oppose Polycomb within minutes, leading to activation of bivalent gene transcription in mouse embryonic stem cells...
September 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28916733/clonal-expansion-and-epigenetic-reprogramming-following-deletion-or-amplification-of-mutant-idh1
#8
Tali Mazor, Charles Chesnelong, Aleksandr Pankov, Llewellyn E Jalbert, Chibo Hong, Josie Hayes, Ivan V Smirnov, Roxanne Marshall, Camila F Souza, Yaoqing Shen, Pavithra Viswanath, Houtan Noushmehr, Sabrina M Ronen, Steven J M Jones, Marco A Marra, J Gregory Cairncross, Arie Perry, Sarah J Nelson, Susan M Chang, Andrew W Bollen, Annette M Molinaro, Henrik Bengtsson, Adam B Olshen, Samuel Weiss, Joanna J Phillips, H Artee Luchman, Joseph F Costello
IDH1 mutation is the earliest genetic alteration in low-grade gliomas (LGGs), but its role in tumor recurrence is unclear. Mutant IDH1 drives overproduction of the oncometabolite d-2-hydroxyglutarate (2HG) and a CpG island (CGI) hypermethylation phenotype (G-CIMP). To investigate the role of mutant IDH1 at recurrence, we performed a longitudinal analysis of 50 IDH1 mutant LGGs. We discovered six cases with copy number alterations (CNAs) at the IDH1 locus at recurrence. Deletion or amplification of IDH1 was followed by clonal expansion and recurrence at a higher grade...
September 15, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28916718/potential-sperm-contributions-to-the-murine-zygote-predicted-by-in-silico-analysis
#9
Panagiotis Ntostis, Deborah Carter, David Iles, J D Huntriss, Maria Tzetis, David Miller
Paternal contributions to the zygote are thought to extend beyond delivery of the genome and paternal RNAs have been linked to epigenetic transgenerational inheritance in different species. In addition, sperm-egg fusion activates several downstream processes that contribute to zygote formation, including PLC zeta-mediated egg activation and maternal RNA clearance. Since a third of the preimplantation developmental period in the mouse occurs prior to the first cleavage stage, there is ample time for paternal RNAs or their encoded proteins potentially to interact and participate in early zygotic activities...
September 15, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28916717/nlrps-the-subcortical-maternal-complex-and-genomic-imprinting
#10
David Monk, Marta Sanchez-Delgado, Rosemary Fisher
Before activation of the embryonic genome, the oocyte provides many of the RNAs and proteins required for the epigenetic reprogramming and the transition to a totipotent state. Targeted disruption of a subset of oocyte-derived transcripts in mice results in early embryonic lethality and cleavage stage embryonic arrest as highlighted by the members of the Subcortical Maternal Complex (SCMC). Maternal-effect recessive mutations of NLRP7, KHDC3L and NLRP5 in humans are associated with variable reproductive outcomes, biparental hydatidiform moles (BiHM) and widespread multi-locus imprinting disturbances...
September 15, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28916652/lsd1-mediated-epigenetic-reprogramming-drives-cenpe-expression-and-prostate-cancer-progression
#11
Yi Liang, Musaddeque Ahmed, Haiyang Guo, Fraser Soares, Junjie T Hua, Shuai Gao, Catherine Lu, Christine Poon, Wanting Han, Jens Langstein, Muhammad B Ekram, Brian Li, Elai Davicioni, Mandeep Takhar, Nicholas Erho, R Jeffrey Karnes, Dianne Chadwick, Theodorus van der Kwast, Paul C Boutros, Cheryl H Arrowsmith, Felix Y Feng, Anthony Michael Joshua, Amina Zoubeidi, Changmeng Cai, Housheng H He
Androgen receptor (AR) signaling is a key driver of prostate cancer (PCa), and androgen-deprivation therapy (ADT) is a standard treatment for patients with advanced and metastatic disease. However, patients receiving ADT eventually develop incurable castration-resistant PCa (CRPC). Here we report that the chromatin modifier LSD1, an important regulator of AR transcriptional activity, undergoes epigenetic reprogramming in CRPC. LSD1 reprogramming in this setting activated a subset of cell cycle genes including CENPE, a centromere binding protein and mitotic kinesin...
September 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28916632/tissue-sex-and-age-specific-dna-methylation-of-rat-glucocorticoid-receptor-gene-promoter-and-insulin-like-growth-factor-2-imprinting-control-region
#12
Ogechukwu Brenda Agba, Ludwig Lausser, Klaus Huse, Christoph Bergmeier, Niels Jahn, Marco Groth, Martin Bens, Arne Sahm, Maria Gall, Otto W Witte, Hans A Kestler, Matthias Schwab, Matthias Platzer
Tissue-, sex- and age-specific epigenetic modifications such as DNA methylation are largely unknown. Changes in DNA methylation of the glucocorticoid receptor gene (NR3C1) and imprinting control region (ICR) of IGF2 and H19 genes during the lifespan are particularly interesting since these genes are susceptible to epigenetic modifications by prenatal stress or malnutrition. They are important regulators of development and aging. Methylation changes of NR3C1 affect glucocorticoid receptor expression, which is associated with stress sensitivity and stress-related diseases predominantly occurring during aging...
September 15, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28916494/transflammation-innate-immune-signaling-in-nuclear-reprogramming
#13
Shu Meng, Palas Chanda, Rajarajan A Thandavarayan, John P Cooke
Induction of pluripotency in somatic cells by retroviral overexpression of four transcription factors has revolutionized the field of stem cell biology and regenerative medicine. The efficient induction of pluripotency requires the activation of innate immune signaling in a process termed "transflammation" [1]. Specifically, the stimulation of pattern recognition receptors (PRRs) causes global alterations in the expression and activity of epigenetic modifiers to favor an open chromatin configuration. Activation of toll-like receptors (TLR) or RIG-1-like receptors (RLR) [2] trigger signaling cascades that result in NFκB or IRF-3 mediated changes in epigenetic plasticity that facilitate reprogramming...
September 12, 2017: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/28916376/transcriptome-profiling-of-the-plutella-xylostella-lepidoptera-plutellidae-ovary-reveals-genes-involved-in-oogenesis
#14
Lu Peng, Lei Wang, Yi-Fan Yang, Ming-Min Zou, Wei-Yi He, Yue Wang, Qing Wang, Liette Vasseur, Min-Sheng You
BACKGROUND: As a specialized organ, the insect ovary performs valuable functions by ensuring fecundity and population survival. Oogenesis is the complex physiological process resulting in the production of mature eggs, which are involved in epigenetic programming, germ cell behavior, cell cycle regulation, etc. Identification of the genes involved in ovary development and oogenesis is critical to better understand the reproductive biology and screening the potential molecular targets in Plutella xylostella, a worldwide destructive pest of economically major crops...
September 12, 2017: Gene
https://www.readbyqxmd.com/read/28916365/sodium-phenylbutyrate-abrogates-african-swine-fever-virus-replication-by-disrupting-the-virus-induced-hypoacetylation-status-of-histone-h3k9-k14
#15
Gonçalo Frouco, Ferdinando B Freitas, Carlos Martins, Fernando Ferreira
African swine fever virus (ASFV) causes a highly lethal disease in swine for which neither a vaccine nor treatment are available. Recently, a new class of drugs that inhibit histone deacetylases enzymes (HDACs) has received an increasing interest as antiviral agents. Considering studies by others showing that valproic acid, an HDAC inhibitor (HDACi), blocks the replication of enveloped viruses and that ASFV regulates the epigenetic status of the host cell by promoting heterochromatinization and recruitment of class I HDACs to viral cytoplasmic factories, the antiviral activity of four HDACi against ASFV was evaluated in this study...
September 12, 2017: Virus Research
https://www.readbyqxmd.com/read/28916331/depressive-like-phenotype-induced-by-prenatal-dexamethasone-in-mice-is-reversed-by-desipramine
#16
Mirko Conti, Stefan Spulber, Marilena Raciti, Sandra Ceccatelli
Exposure to prenatal insults has been associated with an increased risk for neuropsychiatric disorders, including depression, but the mechanisms are still poorly understood. Persistent alterations of the HPA axis feedback mechanism as well as adult impaired neurogenesis are believed to play a relevant role in the etiology of depression. In addition, growing evidence points at epigenetic reprogramming as a key factor. We have previously shown that prenatal exposure to the synthetic glucocorticoid dexamethasone (DEX) impairs neurogenesis and leads to late onset of depression-like behavior that does not respond to the SSRI antidepressant fluoxetine (FLX)...
September 12, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28916223/bet-bromodomain-inhibitors-modulate-epigenetic-patterns-at-the-diacylglycerol-kinase-alpha-enhancer-associated-with-radiation-induced-fibrosis
#17
Gintvile Valinciute, Christoph Weigel, Marlon R Veldwijk, Christopher C Oakes, Carsten Herskind, Frederik Wenz, Christoph Plass, Peter Schmezer, Odilia Popanda
BACKGROUND AND PURPOSE: Fibrosis is a frequent adverse effect of radiotherapy and no effective treatments are currently available to prevent or reverse fibrotic disease. We have previously identified altered epigenetic patterns at a gene enhancer of the diacylglycerol kinase alpha (DGKA) locus in normal skin fibroblasts derived from fibrosis patients. An open chromatin pattern related to radiation-inducibility of DGKA is associated with onset of radiation-induced fibrosis. Here, we explore epigenetic modulation of DGKA as a way to mitigate predisposition to fibrosis...
September 12, 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/28915902/development-and-clinical-application-of-radiomics-in-lung-cancer
#18
REVIEW
Bojiang Chen, Rui Zhang, Yuncui Gan, Lan Yang, Weimin Li
Since the discovery of X-rays at the end of the 19(th) century, medical imageology has progressed for 100 years, and medical imaging has become an important auxiliary tool for clinical diagnosis. With the launch of the human genome project (HGP) and the development of various high-throughput detection techniques, disease exploration in the post-genome era has extended beyond investigations of structural changes to in-depth analyses of molecular abnormalities in tissues, organs and cells, on the basis of gene expression and epigenetics...
September 15, 2017: Radiation Oncology
https://www.readbyqxmd.com/read/28915836/changes-in-dna-methylation-in-na%C3%A3-ve-t-helper-cells-regulate-the-pathophysiological-state-in-minimal-change-nephrotic-syndrome
#19
Yasuko Kobayashi, Akira Aizawa, Takumi Takizawa, Katsuhide Igarashi, Izuho Hatada, Hirokazu Arakawa
BACKGROUND: DNA methylation plays a crucial role in regulating transcription, and changes in DNA methylation affect gene expression and disease development. Minimal change nephrotic syndrome (MCNS) has been reported to involve immunological disturbances. Since the characteristic features of the disease include recurrent relapse and sex and age preference, the disease pathogenesis may be partly related to epigenetic changes. However, little is known about these changes. METHODS: We analyzed genome-wide DNA methylation using the microarray-based integrated analysis of methylation by isoschizomers method...
September 15, 2017: BMC Research Notes
https://www.readbyqxmd.com/read/28915715/epigenetic-regulation-during-the-differentiation-of-stem-cells-to-germ-cells
#20
REVIEW
Yuan-Chao Sun, Yong-Yong Wang, Wei Ge, Shun-Feng Cheng, Paul W Dyce, Wei Shen
Gametogenesis is an essential process to ensure the transfer of genetic information from one generation to the next. It also provides a mechanism by which genetic evolution can take place. Although the genome of primordial germ cells (PGCs) is exactly the same with somatic cells within an organism, there are significant differences between their developments. For example, PGCs eventually undergo meiosis to become functional haploid gametes, and prior to that they undergo epigenetic imprinting which greatly alter their genetic regulation...
August 22, 2017: Oncotarget
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