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epigenetic regulation

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https://www.readbyqxmd.com/read/29457966/combined-treatment-with-valproic-acid-and-5-aza-2-deoxycytidine-synergistically-inhibits-human-clear-cell-renal-cell-carcinoma-growth-and-migration
#1
Wenjin Xi, Xu Chen, Jinbo Sun, Wei Wang, Yi Huo, Guoxu Zheng, Jieheng Wu, Yufang Li, Angang Yang, Tao Wang
BACKGROUND Histone acetylation and DNA methylation are important mammalian epigenetic modifications that participate in the regulation of gene expression. Because dysregulation of histone deacetylase and DNA methyltransferases are hallmarks of malignancy, they have become promising therapeutic targets. In this study, we explored the anti-tumor activity of valproic acid (VPA), a histone deacetylase inhibitor (HDACi) and 5-Aza-2'-deoxycytidine (5-Aza), an inhibitor of DNA methyltransferases, on renal cell carcinoma (RCC) cell lines 786-O and 769-P...
February 19, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29457784/hiv-latency-is-reversed-by-acss2-driven-histone-crotonylation
#2
Guochun Jiang, Don Nguyen, Nancie M Archin, Steven A Yukl, Gema Méndez-Lagares, Yuyang Tang, Maher M Elsheikh, George R Thompson, Dennis J Hartigan-O'Connor, David M Margolis, Joseph K Wong, Satya Dandekar
Eradication of HIV-1 (HIV) is hindered by stable viral reservoirs. Viral latency is epigenetically regulated. While the effects of histone acetylation and methylation at the HIV long-terminal repeat (LTR) have been described, our knowledge of the proviral epigenetic landscape is incomplete. We report that a previously unrecognized epigenetic modification of the HIV LTR, histone crotonylation, is a regulator of HIV latency. Reactivation of latent HIV was achieved following the induction of histone crotonylation through increased expression of the crotonyl-CoA-producing enzyme acyl-CoA synthetase short-chain family member 2 (ACSS2)...
February 19, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29456718/molecular-challenges-of-neuroendocrine-tumors
#3
Parthik Patel, Karina Galoian
Neuroendocrine tumors (NETs) are a very heterogeneous group that are thought to originate from the cells of the endocrine and nervous systems. These tumors develop in a number of organs, predominantly in the gastrointestinal and pulmonary systems. Clinical detection and diagnosis are reliable at the late stages when metastatic spread has occurred. However, traditional conventional therapies such as radiation and chemotherapy are not effective. In the majority of cases even surgical resection at that stage is unlikely to produce promising reusults...
March 2018: Oncology Letters
https://www.readbyqxmd.com/read/29456549/global-dna-methylation-in-the-chestnut-blight-fungus-cryphonectria-parasitica-and-genome-wide-changes-in-dna-methylation-accompanied-with-sectorization
#4
Kum-Kang So, Yo-Han Ko, Jeesun Chun, Jyotiranjan Bal, Junhyun Jeon, Jung-Mi Kim, Jaeyoung Choi, Yong-Hwan Lee, Jin Hoe Huh, Dae-Hyuk Kim
Mutation in CpBck1 , an ortholog of the cell wall integrity mitogen-activated protein kinase kinase kinase (MAPKKK) of Saccharomyces cerevisiae , in the chestnut blight fungus Cryphonectria parasitica resulted in a sporadic sectorization as culture proceeded. The progeny from the sectored area maintained the characteristics of the sector, showing a massive morphogenetic change, including robust mycelial growth without differentiation. Epigenetic changes were investigated as the genetic mechanism underlying this sectorization...
2018: Frontiers in Plant Science
https://www.readbyqxmd.com/read/29456384/tea-polyphenols-and-prevention-of-epigenetic-aberrations-in-cancer
#5
REVIEW
Arundhati Bag, Niladri Bag
Tea polyphenols are secondary metabolites of tea plants and are well known for beneficial health effects. They can protect from a variety of illnesses including cancers. Tea polyphenols can prevent cancer by modulating epigenetic aberrations taking place in DNA methylation, histone modifications, and micro-RNAs. By altering these epimutations, they regulate chromatin dynamics and expression of genes those induce or suppress cancer formation. However, majority of the studies in existing literature are carried out for green tea polyphenols rather than black tea polyphenols despite the fact that black tea is the most commonly consumed form of tea (78%) followed by green tea (20%) and other forms of tea...
January 2018: Journal of Natural Science, Biology, and Medicine
https://www.readbyqxmd.com/read/29456180/ras-regulates-the-transition-from-naive-to-primed-pluripotent-stem-cells
#6
Anna Altshuler, Mila Verbuk, Swarnabh Bhattacharya, Ifat Abramovich, Roni Haklai, Jacob H Hanna, Yoel Kloog, Eyal Gottlieb, Ruby Shalom-Feuerstein
The transition from naive to primed state of pluripotent stem cells is hallmarked by epithelial-mesenchymal transition, metabolic switch from oxidative phosphorylation to aerobic glycolysis, and changes in the epigenetic landscape. Since these changes are also seen as putative hallmarks of neoplastic cell transformation, we hypothesized that oncogenic pathways may be involved in this process. We report that the activity of RAS is repressed in the naive state of mouse embryonic stem cells (ESCs) and that all three RAS isoforms are significantly activated upon early differentiation induced by LIF withdrawal, embryoid body formation, or transition to the primed state...
February 8, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29456074/histone-deacetylases-hdacs-as-therapeutic-target-for-depressive-disorders
#7
REVIEW
Paulina Misztak, Patrycja Pańczyszyn-Trzewik, Magdalena Sowa-Kućma
Major depressive disorder (MDD) represents approximately 40% of the disability caused by mental illnesses globally. The poorly understood pathophysiology and limited efficiency of pharmacological treatment (based primarily on the principles of the monoaminergic hypothesis) make depression a serious medical, public and socio-economical problem. An increasing number of studies suggest that epigenetic modifications (alterations in gene expression that are not due to changes in DNA sequence) in certain brain regions and neural circuits represent a key mechanism through which environmental factors interact with individual's genetic constitution to affect risk of mental disorders...
August 12, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/29455658/receptor-tyrosine-kinases-rtks-in-breast-cancer-signaling-therapeutic-implications-and-challenges
#8
REVIEW
Ramesh Butti, Sumit Das, Vinoth Prasanna Gunasekaran, Amit Singh Yadav, Dhiraj Kumar, Gopal C Kundu
Breast cancer is a multifactorial disease and driven by aberrant regulation of cell signaling pathways due to the acquisition of genetic and epigenetic changes. An array of growth factors and their receptors is involved in cancer development and metastasis. Receptor Tyrosine Kinases (RTKs) constitute a class of receptors that play important role in cancer progression. RTKs are cell surface receptors with specialized structural and biological features which respond to environmental cues by initiating appropriate signaling cascades in tumor cells...
February 19, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29455645/pyruvate-kinase-m2-fuels-multiple-aspects-of-cancer-cells-from-cellular-metabolism-transcriptional-regulation-to-extracellular-signaling
#9
REVIEW
Ming-Chuan Hsu, Wen-Chun Hung
Originally identified as a metabolic enzyme that catalyzes the transfer of a phosphate group from phosphoenolpyruvate (PEP) to ADP in the glycolytic pathway, pyruvate kinase M2-type (PKM2) has been shown to exhibit novel biological activities in the nucleus and outside the cells. Although cell-based studies reveal new non-canonical functions of PKM2 in gene transcription, epigenetic modulation and cell cycle progression, the importance of these non-canonical functions in PKM2-mediated tumorigenesis is still under debate because studies in genetically modified mice do not consistently echo the findings observed in cultured cancer cells...
February 19, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29455435/dna-methylation-regulated-micrornas-in-hpv-16-induced-head-and-neck-squamous-cell-carcinoma-hnscc
#10
M K Sannigrahi, Rajni Sharma, Varinder Singh, Naresh K Panda, Vidya Rattan, Madhu Khullar
INTRODUCTION: Epigenetic modifications have been reported to play an important role in regulating gene expression and these modifications become critical when they have a role in controlling another important layer of epigenetic regulation namely microRNAs. In the present study, we have identified the microRNAs that may be regulated by promoter DNA methylation and histone acetylation in Human papilloma virus-positive head and neck squamous cell carcinoma. METHODOLOGY: HPV-negative cell line (UPCI:SCC-116) and HPV-16 +ve cell line (UPCI:SCC-090) were treated with methylation inhibitor (5-aza-2'-deoxycytidine, AZA) and acetylation inhibitor (Trichostatin-A, TSA), followed by micro-array analysis...
February 17, 2018: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29455143/the-birth-and-death-of-effectors-in-rapidly-evolving-filamentous-pathogen-genomes
#11
REVIEW
Simone Fouché, Clémence Plissonneau, Daniel Croll
Plant pathogenic fungi and oomycetes are major risks to food security due to their evolutionary success in overcoming plant defences. Pathogens produce effectors to interfere with host defences and metabolism. These effectors are often encoded in rapidly evolving compartments of the genome. We review how effector genes emerged and were lost in pathogen genomes drawing on the links between effector evolution and chromosomal rearrangements. Some new effectors entered pathogen genomes via horizontal transfer or introgression...
February 15, 2018: Current Opinion in Microbiology
https://www.readbyqxmd.com/read/29454939/comparative-analysis-of-immune-cells-reveals-a-conserved-regulatory-lexicon
#12
Elisa Donnard, Pranitha Vangala, Shaked Afik, Sean McCauley, Anetta Nowosielska, Alper Kucukural, Barbara Tabak, Xiaopeng Zhu, William Diehl, Patrick McDonel, Nir Yosef, Jeremy Luban, Manuel Garber
Most well-characterized enhancers are deeply conserved. In contrast, genome-wide comparative studies of steady-state systems showed that only a small fraction of active enhancers are conserved. To better understand conservation of enhancer activity, we used a comparative genomics approach that integrates temporal expression and epigenetic profiles in an innate immune system. We found that gene expression programs diverge among mildly induced genes, while being highly conserved for strongly induced genes. The fraction of conserved enhancers varies greatly across gene expression programs, with induced genes and early-response genes, in particular, being regulated by a higher fraction of conserved enhancers...
January 30, 2018: Cell Systems
https://www.readbyqxmd.com/read/29453977/amelioration-of-progressive-autoimmune-encephalomyelitis-by-epigenetic-regulation-involves-selective-repression-of-mature-neutrophils-during-the-preclinical-phase
#13
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/29453678/differential-expression-of-the-tweak-receptor-fn14-in-idh1-wild-type-and-mutant-gliomas
#14
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/29453320/methylation-of-the-hoxa10-promoter-directs-mir-196b-5p-dependent-cell-proliferation-and-invasion-of-gastric-cancer-cells
#15
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
#16
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/29453221/h3k9-demethylase-kdm4e-is-an-epigenetic-regulator-for-bovine-embryonic-development-and-a-defective-factor-for-nuclear-reprogramming
#17
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
#18
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
#19
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
#20
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
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