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https://www.readbyqxmd.com/read/29453977/amelioration-of-progressive-autoimmune-encephalomyelitis-by-epigenetic-regulation-involves-selective-repression-of-mature-neutrophils-during-the-preclinical-phase
#1
Arathi Jayaraman, Monica Sharma, Bellur Prabhakar, Mark Holterman, Sundararajan Jayaraman
We have recently demonstrated that treatment of NOD mice with the epigenetic drug Trichostatin A (TSA) ameliorated myelin peptide induced progressive experimental autoimmune encephalomyelitis (P-EAE). Protection was accompanied by induction of antigen-specific T-cell tolerance in the periphery and reduced the influx of T cells into the spinal cord. In this investigation, we examined whether the epigenetic drug could impact the innate immune system as well. Whereas the mature (MHC class II + ) CD11b + Ly-6G + neutrophils expanded substantially in the peripheral lymphoid compartment during the preclinical phase, the MHC class II + , CD11b + Ly-6C + mature monocytes increased modestly throughout the disease course...
February 14, 2018: Experimental Neurology
https://www.readbyqxmd.com/read/29453919/genetic-and-epigenetic-differences-of-benign-and-malignant-pheochromocytomas-and-paragangliomas-ppgls
#2
Fatemeh Khatami, Mahsa Mohammadamoli, Seyed Mohammad Tavangar
Pheochromocytomas and paragangliomas (PPGLs) are tumors arising from the adrenal medulla and sympathetic/parasympathetic paraganglia, respectively. According to Th e Cancer Genome Atlas (TCGA), approximately 40% of PPGLs are due to germ line mutations in one of 16 susceptibility genes, and a further 30% are due to somatic alterations in at least seven main genes (VHL, EPAS1, CSDE1, MAX, HRAS, NF1, RET, and possibly KIF1B). Th e diagnosis of malignant PPGL was straight forward in most cases as it was defined as presence of PPGL in non-chromaffin tissues...
January 1, 2018: Endocrine Regulations
https://www.readbyqxmd.com/read/29453678/differential-expression-of-the-tweak-receptor-fn14-in-idh1-wild-type-and-mutant-gliomas
#3
David S Hersh, Sen Peng, Jimena G Dancy, Rebeca Galisteo, Jennifer M Eschbacher, Rudy J Castellani, Jonathan E Heath, Teklu Legesse, Anthony J Kim, Graeme F Woodworth, Nhan L Tran, Jeffrey A Winkles
The TNF receptor superfamily member Fn14 is overexpressed by many solid tumor types, including glioblastoma (GBM), the most common and lethal form of adult brain cancer. GBM is notable for a highly infiltrative growth pattern and several groups have reported that high Fn14 expression levels can increase tumor cell invasiveness. We reported previously that the mesenchymal and proneural GBM transcriptomic subtypes expressed the highest and lowest levels of Fn14 mRNA, respectively. Given the recent histopathological re-classification of human gliomas by the World Health Organization based on isocitrate dehydrogenase 1 (IDH1) gene mutation status, we extended this work by comparing Fn14 gene expression in IDH1 wild-type (WT) and mutant (R132H) gliomas and in cell lines engineered to overexpress the IDH1 R132H enzyme...
February 16, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29453446/environmental-genetic-and-epigenetic-contributions-to-cocaine-addiction
#4
REVIEW
R Christopher Pierce, Bruno Fant, Sarah E Swinford-Jackson, Elizabeth A Heller, Wade H Berrettini, Mathieu E Wimmer
Decades of research on cocaine has produced volumes of data that have answered many important questions about the nature of this highly addictive drug. Sadly, none of this information has translated into the development of effective therapies for the treatment of cocaine addiction. This review endeavors to assess the current state of cocaine research in an attempt to identify novel pathways for therapeutic development. For example, risk of cocaine addiction is highly heritable but genome-wide analyses comparing cocaine-dependent individuals to controls have not resulted in promising targets for drug development...
February 5, 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29453320/methylation-of-the-hoxa10-promoter-directs-mir-196b-5p-dependent-cell-proliferation-and-invasion-of-gastric-cancer-cells
#5
Linlin Shao, Zheng Chen, Dunfa Peng, Mohammed Soutto, Shoumin Zhu, Andreia Bates, Shutian Zhang, Wael El-Rifai
The cross-talk between epigenetics and miRNA expression plays an important role in human tumorigenesis. Herein, we investigated the regulation and role of miR-196b-5p in gastric cancer. Using quantitative real-time RT-PCR, we demonstrate that miR-196b-5p is significantly overexpressed in human gastric cancer tissues (P<0.01). In addition, we also found that HOXA10, the host gene for miR-196b-5p, is overexpressed and positively correlated with miR-196b-5p expression levels (P<0.001). Quantitative pyrosequencing methylation analysis of HOXA10 promoter, demonstrated significantly lower levels of promoter DNA methylation of HOXA10 in gastric cancer samples, as compared to normal gastric mucosa samples (non-tumor control)...
February 16, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29453291/lsd1-inhibition-exerts-its-anti-leukemic-effect-by-recommissioning-pu-1-and-c-ebp%C3%AE-dependent-enhancers-in-aml
#6
Monica Cusan, Sheng F Cai, Helai P Mohammad, Andrei Krivtsov, Alan Chramiec, Evangelia Loizou, Matthew D Witkin, Kimberly N Smitheman, Daniel G Tenen, Min Ye, Britta Will, Ulrich Steidl, Ryan G Kruger, Ross L Levine, Hugh Y Rienhoff, Richard P Koche, Scott A Armstrong
Epigenetic regulators are recurrently mutated and aberrantly expressed in acute myeloid leukemia (AML). Targeted therapies designed to inhibit these chromatin-modifying enzymes, such as the histone demethylase lysine specific demethylase 1 (LSD1) and the histone methyltransferase DOT1L, have been developed as novel treatment modalities for these often refractory diseases. A common feature of many of these targeted agents is their ability to induce myeloid differentiation, suggesting that multiple paths toward a myeloid gene expression program can be engaged to relieve the differentiation blockade that is uniformly seen in AML...
February 16, 2018: Blood
https://www.readbyqxmd.com/read/29453249/hhex-induces-promyelocyte-self-renewal-and-cooperates-with-growth-factor-independence-to-cause-myeloid-leukemia-in-mice
#7
Jacob T Jackson, Ashley P Ng, Benjamin J Shields, Sue Haupt, Ygal Haupt, Matthew P McCormack
The hematopoietically expressed homeobox (Hhex) transcription factor is overexpressed in human myeloid leukemias. Conditional knockout models of murine acute myeloid leukemia indicate that Hhex maintains leukemia stem cell self-renewal by enabling Polycomb-mediated epigenetic repression of the Cdkn2a tumor suppressor locus, encoding p16 Ink4a and p19 Arf However, whether Hhex overexpression also affects hematopoietic differentiation is unknown. To study this, we retrovirally overexpressed Hhex in hematopoietic progenitors...
February 27, 2018: Blood Advances
https://www.readbyqxmd.com/read/29453221/h3k9-demethylase-kdm4e-is-an-epigenetic-regulator-for-bovine-embryonic-development-and-a-defective-factor-for-nuclear-reprogramming
#8
Xin Liu, Yizhi Wang, Yuanpeng Gao, Jianmin Su, Jingcheng Zhang, Xupeng Xing, Chuan Zhou, Kezhen Yao, Quanli An, Yong Zhang
Aberrant epigenetic reprogramming often results in developmental defects in somatic cell nuclear transfer (SCNT) embryos during embryonic genome activation (EGA). Bovine eight-cell SCNT embryos exhibit global hypermethylation of histone H3 lysine 9 tri- and di-methylation (H3K9me3/2), but the intrinsic reason for this remains elusive. Here, we provide evidence that two H3K9 demethylase genes, lysine-specific demethylase 4D ( KDM4D ) and 4E ( KDM4E ), are related to active H3K9me3/2 demethylation in in vitro fertilized (IVF) embryos and are deficiently expressed in cloned embryos at the time of EGA...
February 16, 2018: Development
https://www.readbyqxmd.com/read/29452952/phasevarions-of-bacterial-pathogens-methylomics-sheds-new-light-on-old-enemies
#9
REVIEW
John M Atack, Aimee Tan, Lauren O Bakaletz, Michael P Jennings, Kate L Seib
A wide variety of bacterial pathogens express phase-variable DNA methyltransferases that control expression of multiple genes via epigenetic mechanisms. These randomly switching regulons - phasevarions - regulate genes involved in pathogenesis, host adaptation, and antibiotic resistance. Individual phase-variable genes can be identified in silico as they contain easily recognized features such as simple sequence repeats (SSRs) or inverted repeats (IRs) that mediate the random switching of expression. Conversely, phasevarion-controlled genes do not contain any easily identifiable features...
February 13, 2018: Trends in Microbiology
https://www.readbyqxmd.com/read/29452937/epigenetic-chromatin-modification-by-amber-suppression-technology
#10
REVIEW
Heinz Neumann, Petra Neumann-Staubitz, Anna Witte, Daniel Summerer
The genetic incorporation of unnatural amino acids (UAAs) into proteins by amber suppression technology provides unique avenues to study protein structure, function and interactions both in vitro and in living cells and organisms. This approach has been particularly useful for studying mechanisms of epigenetic chromatin regulation, since these extensively involve dynamic changes in structure, complex formation and posttranslational modifications that are difficult to access by traditional approaches. Here, we review recent achievements in this field, emphasizing UAAs that help to unravel protein-protein interactions in cells by photo-crosslinking or that allow the biosynthesis of proteins with defined posttranslational modifications for studying their function and turnover in vitro and in cells...
February 13, 2018: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/29452935/e3-ligase-vhl-promotes-group-2-innate-lymphoid-cell-maturation-and-function-via-glycolysis-inhibition-and-induction-of-interleukin-33-receptor
#11
Qian Li, Dulei Li, Xian Zhang, Qingqing Wan, Wen Zhang, Mingke Zheng, Le Zou, Chris Elly, Jee H Lee, Yun-Cai Liu
Group 2 innate lymphoid cells (ILC2s) are a specialized subset of lymphoid effector cells that are critically involved in allergic responses; however, the mechanisms of their regulation remain unclear. We report that conditional deletion of the E3 ubiquitin ligase VHL in innate lymphoid progenitors minimally affected early-stage bone marrow ILC2s but caused a selective and intrinsic decrease in mature ILC2 numbers in peripheral non-lymphoid tissues, resulting in reduced type 2 immune responses. VHL deficiency caused the accumulation of hypoxia-inducible factor 1α (HIF1α) and attenuated interleukin-33 (IL-33) receptor ST2 expression, which was rectified by HIF1α ablation or inhibition...
February 6, 2018: Immunity
https://www.readbyqxmd.com/read/29452898/transcriptional-and-epigenetic-regulation-of-innate-like-t-lymphocyte-development
#12
REVIEW
Mihalis Verykokakis, Barbara L Kee
Invariant Natural Killer T (iNKT) cells are a heterogeneous innate T cell population that recognizes lipid antigens. Despite the monospecific nature of their T cell receptor, iNKT cells differentiate into stable sublineages during thymic development, before foreign antigen encounter. How iNKT cell subsets acquire and maintain their functional programs is a central question in innate lymphocyte biology. Global transcriptional and epigenetic profiling of iNKT subsets has provided insights into the internal wiring of these subsets that defines their identity...
February 13, 2018: Current Opinion in Immunology
https://www.readbyqxmd.com/read/29452791/untapped-reserves-controlling-primordial-follicle-growth-activation
#13
REVIEW
Amanda Kallen, Alex J Polotsky, Joshua Johnson
Even with the benefit of assisted reproductive technologies (ART), many women are unable to conceive and deliver healthy offspring. One common cause of infertility is the inability to produce eggs capable of contributing to live birth. This can occur despite standard-of-care treatment to maximize the recovery of eggs from growing ovarian follicles. Dormant primordial follicles in the human ovary are a 'reserve ' that can be exploited clinically to overcome this problem. We discuss how controlling primordial follicle growth activation (PFGA) can produce increased numbers of high-quality eggs available for fertility treatment(s)...
February 13, 2018: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/29452766/traumatic-stress-and-accelerated-dna-methylation-age-a-meta-analysis
#14
Erika J Wolf, Hannah Maniates, Nicole Nugent, Adam X Maihofer, Don Armstrong, Andrew Ratanatharathorn, Allison E Ashley-Koch, Melanie Garrett, Nathan A Kimbrel, Adriana Lori, Va Mid-Atlantic Mirecc Workgroup, Allison E Aiello, Dewleen G Baker, Jean C Beckham, Marco P Boks, Sandro Galea, Elbert Geuze, Michael A Hauser, Ronald C Kessler, Karestan C Koenen, Mark W Miller, Kerry J Ressler, Victoria Risbrough, Bart P F Rutten, Murray B Stein, Robert J Ursano, Eric Vermetten, Christiaan H Vinkers, Monica Uddin, Alicia K Smith, Caroline M Nievergelt, Mark W Logue
BACKGROUND: Recent studies examining the association between posttraumatic stress disorder (PTSD) and accelerated aging, as defined by DNA methylation-based estimates of cellular age that exceed chronological age, have yielded mixed results. METHODS: We conducted a meta-analysis of trauma exposure and PTSD diagnosis and symptom severity in association with accelerated DNA methylation age using data from 9 cohorts contributing to the Psychiatric Genomics Consortium PTSD Epigenetics Workgroup (combined N = 2186)...
December 27, 2017: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/29452666/transformation-of-follicular-lymphoma-why-does-it-happen-and-can-it-be-prevented
#15
REVIEW
Brian K Link
Follicular lymphoma is a clinical disease with a multitude of presentations and behaviors. Although infrequent, transformation of follicular lymphoma to a more aggressive behaving subtype - prototypically diffuse large B-cell lymphoma - confers a substantially adverse prognosis. There is no consensus for optimal management after transformation is recognized. Historically considered a distinct clinical event, this review highlights the multiple subclinical transformational events that either variably or cumulatively result in clinical recognition of transformed follicular lymphoma...
March 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29452665/novel-agents-for-relapsed-and-refractory-follicular-lymphoma
#16
REVIEW
Chan Yoon Cheah, Nathan H Fowler
Follicular lymphoma is one of the most common non-Hodgkin's lymphomas. Although current frontline regimens are associated with high response rates, most patients still relapse. When progression is discovered, re-establishing the diagnosis and ruling out transformation in paramount. The outcomes following relapse have been improving due to the activity and increasing availability of novel agents with various mechanisms of action. Despite these advances, single agent activity is limited and the disease remains incurable in the majority of cases...
March 2018: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29452418/phf20-collaborates-with-parp1-to-promote-stemness-and-aggressiveness-of-neuroblastoma-cells-through-activation-of-sox2-and-oct4
#17
Wenyong Long, Wei Zhao, Bo Ning, Jing Huang, Junjun Chu, Linfeng Li, Qianquan Ma, Changsheng Xing, Helen Y Wang, Qing Liu, Rong-Fu Wang
The differentiation status of neuroblastoma (NB) strongly correlates with its clinical outcomes; however, the molecular mechanisms driving maintenance of stemness and differentiation remain poorly understood. Here, we show that plant homeodomain finger-containing protein 20 (PHF20) functions as a critical epigenetic regulator in sustaining stem cell-like phenotype of NB by using CRISPR/Cas9-based targeted knockout (KO) for high-throughput screening of gene function in NB cell differentiation. Expression of PHF20 in NB was significantly associated with high aggressiveness of the tumor and poor outcomes for NB patients...
February 14, 2018: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/29452350/extra-virgin-olive-oil-contains-a-metabolo-epigenetic-inhibitor-of-cancer-stem-cells
#18
Bruna Corominas-Faja, Elisabet Cuyàs, Jesús Lozano-Sánchez, Sílvia Cufí, Sara Verdura, Salvador Fernández-Arroyo, Isabel Borrás-Linares, Begoña Martin-Castillo, Ángel G Martin, Ruth Lupu, Alfons Nonell-Canals, Melchor Sanchez-Martinez, Vicente Micol, Jorge Joven, Antonio Segura-Carretero, Javier A Menendez
Targeting tumor-initiating, drug-resistant populations of cancer stem cells (CSC) with phytochemicals is a novel paradigm for cancer prevention and treatment. We herein employed a phenotypic drug discovery approach coupled to mechanism-of-action profiling and target deconvolution to identify phenolic components of extra virgin olive oil (EVOO) capable of suppressing the functional traits of CSC in breast cancer (BC). In vitro screening revealed that the secoiridoid decarboxymethyl oleuropein aglycone (DOA) could selectively target sub-populations of epithelial-like, aldehyde dehydrogenase (ALDH)-positive and mesenchymal-like, CD44+CD24-/low CSC...
February 14, 2018: Carcinogenesis
https://www.readbyqxmd.com/read/29452261/maternal-betaine-administration-modulates-hepatic-type-1-iodothyronine-deiodinase-dio1-expression-in-chicken-offspring-through-epigenetic-modifications
#19
Zhen Hou, Qinwei Sun, Yun Hu, Shu Yang, Yibo Zong, Ruqian Zhao
As a feed additive, betaine is widely used in livestock production for its ability to promote growth. Our previous studies had reported that maternal betaine supplementation altered hepatic metabolism in offspring. But it remains unknown whether and how maternal betaine modulates metabolism of thyroid hormones in the offspring chickens by epigenetic modification. In this study, one hundred and twenty Rugao yellow-feathered laying hens were randomly divided into two groups, and were fed basal diet with or without 0...
February 13, 2018: Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology
https://www.readbyqxmd.com/read/29451908/cas9-mediated-excision-of-proximal-dnasei-h3k4me3-signatures-confers-robust-silencing-of-microrna-and-long-non-coding-rna-genes
#20
Harshavardhan Janga, Marina Aznaourova, Fabian Boldt, Katrin Damm, Arnold Grünweller, Leon N Schulte
CRISPR/Cas9-based approaches have greatly facilitated targeted genomic deletions. Contrary to coding genes however, which can be functionally knocked out by frame-shift mutagenesis, non-coding RNA (ncRNA) gene knockouts have remained challenging. Here we present a universal ncRNA knockout approach guided by epigenetic hallmarks, which enables robust gene silencing even in provisionally annotated gene loci. We build on previous work reporting the presence of overlapping histone H3 lysine 4 tri-methylation (H3K4me3) and DNaseI hypersensitivity sites around the transcriptional start sites of most genes...
2018: PloS One
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