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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/29457866/epigenetic-effects-of-metformin-from-molecular-mechanisms-to-clinical-implications
#2
REVIEW
S C Bridgeman, G C Ellison, P E Melton, P Newsholme, Cds Mamotte
There is a growing body of evidence that links epigenetic modifications to type 2 diabetes. Researchers have more recently investigated effects of commonly used medications, including those prescribed for diabetes, on epigenetic processes. This work reviews the influence of the widely used antidiabetic drug metformin on epigenomics, microRNA levels and subsequent gene expression and potential clinical implications. Metformin may influence the activity of numerous epigenetic modifying enzymes, mostly via modulating the activation of AMP-activated protein kinase (AMPK)...
February 19, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29457784/hiv-latency-is-reversed-by-acss2-driven-histone-crotonylation
#3
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/29457186/recognition-of-shorter-and-longer-trimethyllysine-analogues-by-epigenetic-reader-proteins
#4
Abbas H K Al Temimi, Roman Belle, Kiran Kumar, Jordi Poater, Peter Betlem, Bas J G E Pieters, Robert S Paton, F Matthias Bickelhaupt, Jasmin Mecinović
Histone Nε -lysine methylation is a widespread posttranslational modification that is specifically recognised by a diverse class of Nε -methyllysine binding reader proteins. Combined thermodynamic data, molecular dynamics simulations, and quantum chemical studies reveal that reader proteins efficiently bind trimethylornithine and trimethylhomolysine, the simplest Nε -trimethyllysine analogues that differ in the length of the side chain.
February 19, 2018: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/29456765/peripheral-blood-epi-signature-of-claes-jensen-syndrome-enables-sensitive-and-specific-identification-of-patients-and-healthy-carriers-with-pathogenic-mutations-in-kdm5c
#5
Laila C Schenkel, Erfan Aref-Eshghi, Cindy Skinner, Peter Ainsworth, Hanxin Lin, Guillaume Paré, David I Rodenhiser, Charles Schwartz, Bekim Sadikovic
Background: Claes-Jensen syndrome is an X-linked inherited intellectual disability caused by mutations in the KDM5C gene. Kdm5c is a histone lysine demethylase involved in histone modifications and chromatin remodeling. Males with hemizygous mutations in KDM5C present with intellectual disability and facial dysmorphism, while most heterozygous female carriers are asymptomatic. We hypothesized that loss of Kdm5c function may influence other components of the epigenomic machinery including DNA methylation in affected patients...
2018: Clinical Epigenetics
https://www.readbyqxmd.com/read/29456384/tea-polyphenols-and-prevention-of-epigenetic-aberrations-in-cancer
#6
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/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/29455551/effects-of-5-aza-2-deoxycytidine-decitabine-on-gene-expression
#8
Ratnam S Seelan, Partha Mukhopadhyay, M Michele Pisano, Robert M Greene
5-Aza-2'-deoxycytidine (AzaD), also known as Decitabine, is a deoxycytidine analog that is typically used to activate methylated and silenced genes by promoter demethylation. However, a survey of the scientific literature indicates that promoter demethylation may not be the only (or, indeed, the major) mechanism by which AzaD affects gene expression. Regulation of gene expression by AzaD can occur in several ways, including some that are independent of DNA demethylation. Results from several studies indicate that the effect of AzaD on gene expression is highly context-dependent and can differ for the same gene under different environmental settings...
February 18, 2018: Drug Metabolism Reviews
https://www.readbyqxmd.com/read/29455435/dna-methylation-regulated-micrornas-in-hpv-16-induced-head-and-neck-squamous-cell-carcinoma-hnscc
#9
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/29451559/linking-chromatin-dynamics-cell-fate-plasticity-and-tissue-homeostasis-in-adult-mouse-hair-follicle-stem-cells
#10
Jayhun Lee, Tudorita Tumbar
Cellular plasticity for fate acquisition is associated with distinct chromatin states, which include histone modifications, dynamic association of chromatin factors with the DNA, and global chromatin compaction and nuclear organization. While embryonic stem cell (ESC) plasticity in vitro and its link with chromatin states have been characterized in depth, little is known about tissue stem cell plasticity in vivo , during adult tissue homeostasis. Recently, we reported a distinct globally low level of histone H3 K4/9/27me3 in mouse hair follicle stem cells (HFSCs) during quiescence...
July 2017: Mol Life
https://www.readbyqxmd.com/read/29450683/common-adverse-effects-of-novel-therapies-for-multiple-myeloma-mm-and-their-management-strategies
#11
REVIEW
Kristen B McCullough, Miriam A Hobbs, Jithma P Abeykoon, Prashant Kapoor
PURPOSE OF REVIEW: The purpose of this review was to evaluate management strategies for common adverse effects of novel therapies in multiple myeloma (MM), including immunomodulatory drugs, proteasome inhibitors, monoclonal antibodies, and a histone deacetylase inhibitor. RECENT FINDINGS: There are several adverse effects that occur across multiple classes of antimyeloma drugs, including rash, peripheral neuropathy, infusion reactions, and cardiotoxicity, but most can be managed without complete discontinuation of the agent or abandonment of the class...
February 15, 2018: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/29449847/potential-epigenetic-regulation-in-the-germinal-center-reaction-of-lymphoid-tissues-in-hiv-siv-infection
#12
REVIEW
Xiaolei Wang, Huanbin Xu
The production of high-affinity and broadly neutralizing antibodies plays a key role in the defense against pathogens. These antibody responses require effective germinal center (GC) reaction within anatomical niches of GCs, where follicular helper T (Tfh) cells provide cognate help to B cells for T cell-dependent antibody responses. Emerging evidences indicate that GC reaction in normal state and perhaps establishment of latent Tfh cell reservoir in HIV/SIV infection are tightly regulated by epigenetic histone modifications, which are responsible for activating or silencing chromatin...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29447428/uv-b-radiation-delays-flowering-time-through-changes-in-the-prc2-complex-activity-and-mir156-levels-in-arabidopsis-thaliana
#13
Marcela Dotto, María Sol Gómez, María Soledad Soto, Paula Casati
UV-B is a high-energy component of the solar radiation perceived by the plant and induces a number of modifications in plant growth and development, including changes in flowering time. However, the molecular mechanisms underlying these changes are largely unknown. In the present work, we demonstrate that Arabidopsis plants grown under white light supplemented with UV-B show a delay in flowering time, and this developmental reprogramming is mediated by the UVR8 photoreceptor. Using a combination of gene expression analyses and UV-B irradiation of different flowering mutants, we gained insight into the pathways involved in the observed flowering time delay in UV-B exposed Arabidopsis plants...
February 15, 2018: Plant, Cell & Environment
https://www.readbyqxmd.com/read/29447067/regulation-of-eukaryotic-elongation-factor-1-alpha-eef1a-by-dynamic-lysine-methylation
#14
Magnus E Jakobsson, Jędrzej Małecki, Pål Ø Falnes
Lysine methylation is a frequent post-translational protein modification, which has been intensively studied in the case of histone proteins. Lysine methylations are also found on many non-histone proteins, and one prominent example is eukaryotic elongation factor 1 alpha (eEF1A). Besides its essential role in the protein synthesis machinery, a number of non-canonical functions have also been described for eEF1A, such as regulation of the actin cytoskeleton and the promotion of viral replication. The functional significance of the extensive lysine methylations on eEF1A, as well as the identity of the responsible lysine methyltransferases (KMTs), have until recently remained largely elusive...
February 15, 2018: RNA Biology
https://www.readbyqxmd.com/read/29446735/epigenetic-regulation-of-regulatory-t-cells-in-kidney-disease-and-transplantation
#15
Yufeng Liu, Bo Peng, Shengdi Wu, Nuo Xu
Regulatory T (Treg) cells are a kind of immunosuppression cells, which have been used to treat autoimmune diseases and induce allograft tolerance in clinical trials. While Treg cells based therapy is a promising treatment for kidney diseases and an emerging concept for tolerance induction in renal transplantation, a better understanding of the functions and biology of Treg cells is needed to be able to optimally exploit them. Epigenetics regulation, which refers to potentially heritable alterations in gene expression without underlying changes of the nucleotide sequence, plays an important role in Treg cells induction and maintenance...
February 13, 2018: Current Gene Therapy
https://www.readbyqxmd.com/read/29444334/optimized-methods-of-chromatin-immunoprecipitation-chip-for-profiling-histone-modifications-in-industrial-microalgae-nannochloropsis-spp
#16
Li Wei, Jian Xu
Epigenetic factors such as histone modifications play integral roles in plant development and stress response, yet their implications in algae remain poorly understood. In the industrial oleaginous microalgae Nannochloropsis spp., the lack of an efficient methodology for chromatin immunoprecipitation (ChIP), which determines the specific genomic location of various histone modifications, has hindered probing the epigenetic basis of their photosynthetic carbon conversion and storage as oil. Here, a detailed ChIP protocol was developed for Nannochloropsis oceanica, which represents a reliable approach for the analysis of histone modifications, chromatin state, and transcription factor binding sites at the epigenetic level...
February 14, 2018: Journal of Phycology
https://www.readbyqxmd.com/read/29444071/the-phd-finger-protein-spp1-has-distinct-functions-in-the-set1-and-the-meiotic-dsb-formation-complexes
#17
Céline Adam, Raphaël Guérois, Anna Citarella, Laura Verardi, Florine Adolphe, Claire Béneut, Vérane Sommermeyer, Claire Ramus, Jérôme Govin, Yohann Couté, Valérie Borde
Histone H3K4 methylation is a feature of meiotic recombination hotspots shared by many organisms including plants and mammals. Meiotic recombination is initiated by programmed double-strand break (DSB) formation that in budding yeast takes place in gene promoters and is promoted by histone H3K4 di/trimethylation. This histone modification is recognized by Spp1, a PHD-finger containing protein that belongs to the conserved histone H3K4 methyltransferase Set1 complex. During meiosis, Spp1 binds H3K4me3 and interacts with a DSB protein, Mer2, to promote DSB formation close to gene promoters...
February 14, 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29443090/native-chromatin-immunoprecipitation-using-murine-brain-tumor-neurospheres
#18
Flor M Mendez, Felipe J Núñez, Rocío I Zorrilla-Veloz, Pedro R Lowenstein, Maria G Castro
Epigenetic modifications may be involved in the development and progression of glioma. Changes in methylation and acetylation of promoters and regulatory regions of oncogenes and tumor suppressors can lead to changes in gene expression and play an important role in the pathogenesis of brain tumors. Native chromatin immunoprecipitation (ChIP) is a popular technique that allows the detection of modifications or other proteins tightly bound to DNA. In contrast to cross-linked ChIP, in native ChIP, cells are not treated with formaldehyde to covalently link protein to DNA...
January 29, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29443015/isolation-and-cultivation-of-neural-progenitors-followed-by-chromatin-immunoprecipitation-of-histone-3-lysine-79-dimethylation-mark
#19
Patrick Bovio, Deborah Roidl, Stefanie Heidrich, Tanja Vogel, Henriette Franz
Brain development is a complex process, which is controlled in a temporo-spatial manner by gradients of morphogens and different transcriptional programs. Additionally, epigenetic chromatin modifications, like histone methylation, have an important role for establishing and maintaining specific cell fates within this process. The vast majority of histone methylation occurs on the flexible histone tail, which is accessible to histone modifiers, erasers, and histone reader proteins. In contrast, H3K79 methylation is located in the globular domain of histone 3 and is implicated in different developmental functions...
January 26, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29442054/mrna-expression-profiling-of-histone-modifying-enzymes-in-pediatric-acute-monoblastic-leukemia
#20
Pei-Fang Xiao, Yan-Fang Tao, Shao-Yan Hu, Lan Cao, Jun Lu, Jian Wang, Xing Feng, Jian Pan, Yi-Huan Chai
Histone modification is dysregulated in various types of cancers, including hematological malignancies. However, the expression profile of histone-modifying enzymes in pediatric acute monoblastic leukemia (AML FAB M5) has not been investigated. In this study, we evaluated the mRNA expression profile of 85 genes that encode enzymes involved in histone-modification in 27 pediatric AML FAB M5 samples by using a novel real-time PCR array. We obtained a gene cluster consisting of a total of 28 genes (15 up-regulated genes and 13 down-regulated genes)...
March 1, 2017: Die Pharmazie
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