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Epigenetics

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https://www.readbyqxmd.com/read/28346922/epigenetics-in-gastrointestinal-health-and-disease-spotlight-on-dna-methylation-in-the-intestinal-epithelium
#1
Matthias Zilbauer, Judith Kraiczy
Epigenetics can be defined as stable, potentially heritable changes in cellular phenotype caused by mechanisms other than alterations in the underlying DNA sequence. DNA methylation is amongst the most intensely studied epigenetic mechanisms and has been shown to play a major role in regulating fundamental aspects of cell biology including cellular differentiation, organ development, and cell type-specific gene expression. Importantly, it is becoming increasingly clear that epigenetic mechanisms operate at the interface between the genetic code and our environment and are able to mediate environmental changes into stable phenotypic alterations...
2017: Nestlé Nutrition Institute Workshop Series
https://www.readbyqxmd.com/read/28346812/identification-of-a-novel-benzimidazole-pyrazolone-scaffold-that-inhibits-kdm4-lysine-demethylases-and-reduces-proliferation-of-prostate-cancer-cells
#2
David M Carter, Edgar Specker, Jessica Przygodda, Martin Neuenschwander, Jens Peter von Kries, Udo Heinemann, Marc Nazaré, Ulrich Gohlke
Human lysine demethylase (KDM) enzymes (KDM1-7) constitute an emerging class of therapeutic targets, with activities that support growth and development of metastatic disease. By interacting with and co-activating the androgen receptor, the KDM4 subfamily (KDM4A-E) promotes aggressive phenotypes of prostate cancer (PCa). Knockdown of KDM4 expression or inhibition of KDM4 enzyme activity reduces the proliferation of PCa cell lines and highlights inhibition of lysine demethylation as a possible therapeutic method for PCa treatment...
March 1, 2017: SLAS Discov
https://www.readbyqxmd.com/read/28346544/epigenetic-silencing-of-v-d-j-recombination-is-a-major-determinant-for-selective-differentiation-of-mucosal-associated-invariant-t-cells-from-induced-pluripotent-stem-cells
#3
Yutaka Saito, Chie Sugimoto, Toutai Mituyama, Hiroshi Wakao
Mucosal-associated invariant T cells (MAITs) are innate-like T cells that play a pivotal role in the host defense against infectious diseases, and are also implicated in autoimmune diseases, metabolic diseases, and cancer. Recent studies have shown that induced pluripotent stem cells (iPSCs) derived from MAITs selectively redifferentiate into MAITs without altering their antigen specificity. Such a selective differentiation is a prerequisite for the use of MAITs in cell therapy and/or regenerative medicine...
2017: PloS One
https://www.readbyqxmd.com/read/28346453/activity-induced-histone-modifications-govern-neurexin-1-mrna-splicing-and-memory-preservation
#4
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
#5
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
#6
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/28346433/a-cytosolic-ezh1-isoform-modulates-a-prc2-ezh1-epigenetic-adaptive-response-in-postmitotic-cells
#7
Beatrice Bodega, Federica Marasca, Valeria Ranzani, Alessandro Cherubini, Francesco Della Valle, Maria Victoria Neguembor, Michel Wassef, Alessio Zippo, Chiara Lanzuolo, Massimiliano Pagani, Valerio Orlando
The evolution of chromatin-based epigenetic cell memory may be driven not only by the necessity for cells to stably maintain transcription programs, but also by the need to recognize signals and allow plastic responses to environmental stimuli. The mechanistic role of the epigenome in adult postmitotic tissues, however, remains largely unknown. In vertebrates, two variants of the Polycomb repressive complex (PRC2-Ezh2 and PRC2-Ezh1) control gene silencing via methylation of histone H3 on Lys27 (H3K27me). Here we describe a reversible mechanism that involves a novel isoform of Ezh1 (Ezh1β)...
March 27, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28346403/near-infrared-optogenetic-pair-for-protein-regulation-and-spectral-multiplexing
#8
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/28346397/the-process-and-regulatory-components-of-inflammation-in-brain-oncogenesis
#9
REVIEW
A G M Mostofa, Surendra R Punganuru, Hanumantha Rao Madala, Mohammad Al-Obaide, Kalkunte S Srivenugopal
Central nervous system tumors comprising the primary cancers and brain metastases remain the most lethal neoplasms and challenging to treat. Substantial evidence points to a paramount role for inflammation in the pathology leading to gliomagenesis, malignant progression and tumor aggressiveness in the central nervous system (CNS) microenvironment. This review summarizes the salient contributions of oxidative stress, interleukins, tumor necrosis factor-α (TNF-α), cyclooxygenases, and transcription factors such as signal transducer and activator of transcription 3 (STAT3) and nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-κB) and the associated cross-talks to the inflammatory signaling in CNS cancers...
March 27, 2017: Biomolecules
https://www.readbyqxmd.com/read/28346139/oncometabolite-d-2-hydroxyglutarate-enhances-gene-silencing-through-inhibition-of-specific-h3k36-histone-demethylases
#10
Ryan Janke, Anthony Iavarone, Jasper Rine
Certain mutations affecting central metabolism cause accumulation of the oncometabolite D-2-hydroxyglutarate which promotes progression of certain tumors. High levels of D-2-hydroxyglutarate inhibit the TET family of DNA demethylases and Jumonji family of histone demethylases and cause epigenetic changes that lead to altered gene expression. The link between inhibition of DNA demethylation and changes in expression is strong in some cancers, but not in others. To determine whether D-2-hydroxyglutarate can affect gene expression through inhibiting histone demethylases, orthologous mutations to those known to cause accumulation of D-2-hydroxyglutarate in tumors were generated in Saccharomyces cerevisiae, which has histone demethylases but not DNA methylases or demethylases...
March 27, 2017: ELife
https://www.readbyqxmd.com/read/28345661/stepwise-analysis-of-mir9-loci-identifies-mir-9-5p-to-be-involved-in-oestrogen-regulated-pathways-in-breast-cancer-patients
#11
Raffaela Barbano, Barbara Pasculli, Michelina Rendina, Andrea Fontana, Caterina Fusilli, Massimiliano Copetti, Stefano Castellana, Vanna Maria Valori, Maria Morritti, Paolo Graziano, Ciuffreda Luigi, Michelina Coco, Francesco Picardo, Tommaso Mazza, Ella Evron, Roberto Murgo, Evaristo Maiello, Manel Esteller, Vito Michele Fazio, Paola Parrella
miR-9 was initially identified as an epigenetically regulated miRNA in tumours, but inconsistent findings have been reported so far. We analysed the expression of miR-9-5p, miR-9-3p, pri-miRs and MIR9 promoters methylation status in 131 breast cancer cases and 12 normal breast tissues (NBTs). The expression of both mature miRs was increased in tumours as compared to NBTs (P < 0.001) and negatively correlated with ER protein expression (P = 0.005 and P = 0.003, for miR-9-3p and miR-9-5p respectively)...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28345651/epigenome-mapping-highlights-chromatin-mediated-gene-regulation-in-the-protozoan-parasite-trichomonas-vaginalis
#12
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/28345647/sexual-epigenetics-gender-specific-methylation-of-a-gene-in-the-sex-determining-region-of-populus-balsamifera
#13
Katharina Bräutigam, Raju Soolanayakanahally, Marc Champigny, Shawn Mansfield, Carl Douglas, Malcolm M Campbell, Quentin Cronk
Methylation has frequently been implicated in gender determination in plants. The recent discovery of the sex determining region (SDR) of balsam poplar, Populus balsamifera, pinpointed 13 genes with differentiated X and Y copies. We tested these genes for differential methylation using whole methylome sequencing of xylem tissue of multiple individuals grown under field conditions in two common gardens. The only SDR gene to show a marked pattern of gender-specific methylation is PbRR9, a member of the two component response regulator (type-A) gene family, involved in cytokinin signalling...
March 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28345525/tolerance-of-monocytes-and-macrophages-in-response-to-bacterial-endotoxin
#14
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/28345456/overexpression-of-mir-10b-in-colorectal-cancer-patients-correlation-with-twist-1-and-e-cadherin-expression
#15
Rania Abdelmaksoud-Dammak, Nour Chamtouri, Mouna Triki, Amena Saadallah-Kallel, Wajdi Ayadi, Slim Charfi, Abdelmajid Khabir, Lobna Ayadi, Tahia Sallemi-Boudawara, Raja Mokdad-Gargouri
MicroRNAs are emergent players of epigenetics that function as oncogenes or tumor suppressors and that have been implicated in regulating diverse cellular pathways. MiR-10b is an oncogenic microRNA involved in tumor invasion and metastasis in various cancers. Our data have shown that miR-10b is overexpressed in colorectal cancer samples in comparison with non-tumorous adjacent mucosa (p = 0.0025) and that it is associated with severe features such as tumor size >5 cm (p = 0.023), distant metastasis (p = 0...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28345455/recurrent-epigenetic-silencing-of-the-ptprd-tumor-suppressor-in-laryngeal-squamous-cell-carcinoma
#16
Marcin Szaumkessel, Sonia Wojciechowska, Joanna Janiszewska, Natalia Zemke, Ewa Byzia, Katarzyna Kiwerska, Magdalena Kostrzewska-Poczekaj, Adam Ustaszewski, Malgorzata Jarmuz-Szymczak, Reidar Grenman, Malgorzata Wierzbicka, Anna Bartochowska, Krzysztof Szyfter, Maciej Giefing
Cellular processes like differentiation, mitotic cycle, and cell growth are regulated by tyrosine kinases with known oncogenic potential and tyrosine phosphatases that downmodulate the first. Therefore, tyrosine phosphatases are recurrent targets of gene alterations in human carcinomas. We and others suggested recently a tumor suppressor function of the PTPRD tyrosine phosphatase and reported homozygous deletions of the PTPRD locus in laryngeal squamous cell carcinoma. In this study, we investigated other gene-inactivating mechanisms potentially targeting PTPRD, including loss-of-function mutations and also epigenetic alterations like promoter DNA hypermethylation...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28345003/expansion-of-human-tregs-from-cryopreserved-umbilical-cord-blood-for-gmp-compliant-autologous-adoptive-cell-transfer-therapy
#17
Howard R Seay, Amy L Putnam, Judit Cserny, Amanda L Posgai, Emma H Rosenau, John R Wingard, Kate F Girard, Morey Kraus, Angela P Lares, Heather L Brown, Katherine S Brown, Kristi T Balavage, Leeana D Peters, Ashley N Bushdorf, Mark A Atkinson, Jeffrey A Bluestone, Michael J Haller, Todd M Brusko
Umbilical cord blood is a traditional and convenient source of cells for hematopoietic stem cell transplantation. Thymic regulatory T cells (Tregs) are also present in cord blood, and there is growing interest in the use of autologous Tregs to provide a low-risk, fully human leukocyte antigen (HLA)-matched cell product for treating autoimmune diseases, such as type 1 diabetes. Here, we describe a good manufacturing practice (GMP)-compatible Treg expansion protocol using fluorescence-activated cell sorting, resulting in a mean 2,092-fold expansion of Tregs over a 16-day culture for a median yield of 1...
March 17, 2017: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/28344933/precision-medicine-the-golden-gate-for-detection-treatment-and-prevention-of-alzheimer-s-disease
#18
H Hampel, S E O'Bryant, J I Castrillo, C Ritchie, K Rojkova, K Broich, N Benda, R Nisticò, R A Frank, B Dubois, V Escott-Price, S Lista
During this decade, breakthrough conceptual shifts have commenced to emerge in the field of Alzheimer's disease (AD) recognizing risk factors and the non-linear dynamic continuum of complex pathophysiologies amongst a wide dimensional spectrum of multi-factorial brain proteinopathies/neurodegenerative diseases. As is the case in most fields of medicine, substantial advancements in detecting, treating and preventing AD will likely evolve from the generation and implementation of a systematic precision medicine strategy...
December 2016: Journal of Prevention of Alzheimer's Disease
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
#19
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/28344890/suppression-of-indoleamine-2-3-dioxygenase-1-expression-by-promoter-hypermethylation-in-er-positive-breast-cancer
#20
Dyah L Dewi, Soumya R Mohapatra, Saioa Blanco Cabañes, Isabell Adam, Luis F Somarribas Patterson, Bianca Berdel, Masroor Kahloon, Loreen Thürmann, Stefanie Loth, Katharina Heilmann, Dieter Weichenhan, Oliver Mücke, Ines Heiland, Pauline Wimberger, Jan Dominik Kuhlmann, Karl-Heinz Kellner, Sarah Schott, Christoph Plass, Michael Platten, Clarissa Gerhäuser, Saskia Trump, Christiane A Opitz
Kynurenine formation by tryptophan-catabolic indoleamine-2,3-dioxygenase 1 (IDO1) plays a key role in tumor immune evasion and inhibition of IDO1 is efficacious in preclinical models of breast cancer. As the response of breast cancer to immune checkpoint inhibitors may be limited, a better understanding of the expression of additional targetable immunomodulatory pathways is of importance. We therefore investigated the regulation of IDO1 expression in different breast cancer subtypes. We identified estrogen receptor α (ER) as a negative regulator of IDO1 expression...
2017: Oncoimmunology
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