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https://www.readbyqxmd.com/read/28548108/drugging-the-pain-epigenome
#1
REVIEW
Ellen Niederberger, Eduard Resch, Michael J Parnham, Gerd Geisslinger
More than 20% of adults worldwide experience different types of chronic pain, which are frequently associated with several comorbidities and a decrease in quality of life. Several approved painkillers are available, but current analgesics are often hampered by insufficient efficacy and/or severe adverse effects. Consequently, novel strategies for safe, highly efficacious treatments are highly desirable, particularly for chronic pain. Epigenetic mechanisms such as DNA methylation, histone modifications and microRNAs (miRNAs) strongly affect the regulation of gene expression, potentially for long periods over years or even generations, and have been associated with pathophysiological pain...
May 26, 2017: Nature Reviews. Neurology
https://www.readbyqxmd.com/read/28546713/current-concepts-of-epigenetics-in-testicular-cancer
#2
REVIEW
Alfredo Harb-De la Rosa, Meenakkshy Manoharan, Ahmed Saeed Goolam
Testicular germ cell tumors (GCTs) are characterized into seminomas (SGCTs) and non-seminomatous testicular germ cell tumors (NSGCTs). Serum tumor markers (STMs) play an important role in testicular cancer as they provide useful information for diagnosis, staging, and detection of recurrence. Nonetheless, additional tumor markers for early diagnosis and therapeutic options are required to enhance specificity of serological diagnosis of testes cancers. Epigenetics is defined as inherited changes in gene expression that are not encoded in the DNA structure...
June 2017: Indian Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28546575/of-giraffes-necks-and-the-inheritance-of-chromatin-states
#3
Vincenzo Pirrotta
New work reports that both derepressed and hyper-repressed chromatin states in animals can be transmitted to progeny for many generations. Transmission depends on genomic architecture and histone modifications.
May 26, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28546430/crosstalk-between-the-h3k36me3-and-h4k16ac-histone-epigenetic-marks-in-dna-double-strand-break-repair
#4
Lin Li, Yinsheng Wang
Post-translational modifications of histone proteins regulate numerous cellular processes. Among these modifications, trimethylation of lysine 36 in histone H3 (H3K36me3) and acetylation of lysine 16 in histone H4 (H4K16ac) have important roles in transcriptional regulation and DNA damage response signaling. However, whether these two epigenetic histone marks are mechanistically linked remains unclear. Here, we discovered a new pathway through which H3K36me3 stimulates H4K16ac upon DNA double-strand break (DSB) induction in human cells...
May 25, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28546420/alterations-of-histone-modifications-contribute-to-pregnane-x-receptor-mediated-induction-of-cyp3a4-by-rifampicin
#5
Liang Yan, Yiting Wang, Jingyang Liu, Yali Nie, Xiaobo Zhong, Quancheng Kan, Lirong Zhang
Cytochrome P450 3A4 (CYP3A4) is one of the major drug-metabolizing enzymes in human and is responsible for the metabolism of 60% of the clinically used drugs. Many drugs are able to induce the expression of CYP3A4, which usually causes drug-drug interactions and adverse drug reactions. This study aims to explore the role of histone modifications in rifampicin-induced expression of CYP3A4 in LS174T cells. We found that the induction of CYP3A4 mRNA by rifampicin in LS174T cells was associated with increased levels of histone H3 lysine 4 trimethylation (H3K4me3) and H3 acetylation and a decreased level of histone H3 lysine 27 trimethylation (H3K27me3) in the CYP3A4 promoter...
May 25, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28545228/aberrant-dna-methylation-as-a-biomarker-and-a-therapeutic-target-of-cholangiocarcinoma
#6
REVIEW
Toshiaki Nakaoka, Yoshimasa Saito, Hidetsugu Saito
Cholangiocarcinoma is an epithelial malignancy arising in the region between the intrahepatic bile ducts and the ampulla of Vater at the distal end of the common bile duct. The effect of current chemotherapy regimens against cholangiocarcinoma is limited, and the prognosis of patients with cholangiocarcinoma is poor. Aberrant DNA methylation and histone modification induce silencing of tumor suppressor genes and chromosomal instability during carcinogenesis. Studies have shown that the tumor suppressor genes and microRNAs (miRNAs) including MLH1, p14, p16, death-associated protein kinase (DAPK), miR-370 and miR-376c are frequently methylated in cholangiocarcinoma...
May 23, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28542388/targeted-dna-methylation-in-pericentromeres-with-genome-editing-based-artificial-dna-methyltransferase
#7
Taiga Yamazaki, Yu Hatano, Tetsuya Handa, Sakiko Kato, Kensuke Hoida, Rui Yamamura, Takashi Fukuyama, Takayuki Uematsu, Noritada Kobayashi, Hiroshi Kimura, Kazuo Yamagata
To study the impact of epigenetic changes on biological functions, the ability to manipulate the epigenetic status of certain genomic regions artificially could be an indispensable technology. "Epigenome editing" techniques have gradually emerged that apply TALE or CRISPR/Cas9 technologies with various effector domains isolated from epigenetic code writers or erasers such as DNA methyltransferase, 5-methylcytosine oxidase, and histone modification enzymes. Here we demonstrate that a TALE recognizing a major satellite, consisting of a repeated sequence in pericentromeres, could be fused with the bacterial CpG methyltransferase, SssI...
2017: PloS One
https://www.readbyqxmd.com/read/28541490/glanet-genomic-loci-annotation-and-enrichment-tool
#8
Burçak Otlu, Can Firtina, Sündüz Keles, Oznur Tastan
Motivation: Genomic studies identify genomic loci representing genetic variations, transcription factor (TF) occupancy, or histone modification through next generation sequencing (NGS) technologies. Interpreting these loci requires evaluating them with known genomic and epigenomic annotations. Results: We present GLANET as a comprehensive annotation and enrichment analysis tool which implements a sampling-based enrichment test that accounts for GC content and/or mappability biases, jointly or separately...
May 24, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28538738/solid-phase-synthesis-cyclization-and-site-specific-functionalization-of-aziridine-containing-tetrapeptides
#9
Benjamin K W Chung, Christopher J White, Andrei K Yudin
Cyclic tetrapeptides comprise a potent and selective class of molecules with a wide range of biological activities, including the phytotoxic activity of tentoxin and the histone deacetylase (HDAC) inhibitory effects of chlamydocin. The incorporation of a functional aziridine group within cyclic peptides enables their conformational control and allows for late-stage and site-selective functionalization of these molecules, thereby creating the potential for covalent protein labeling. This protocol describes the solid-phase synthesis, cyclization, and site-specific structural modification of aziridine-containing tetrapeptides...
June 2017: Nature Protocols
https://www.readbyqxmd.com/read/28538662/maternal-factors-that-induce-epigenetic-changes-contribute-to-neurological-disorders-in-offspring
#10
REVIEW
Avijit Banik, Deepika Kandilya, Seshadri Ramya, Walter Stünkel, Yap Seng Chong, S Thameem Dheen
It is well established that the regulation of epigenetic factors, including chromatic reorganization, histone modifications, DNA methylation, and miRNA regulation, is critical for the normal development and functioning of the human brain. There are a number of maternal factors influencing epigenetic pathways such as lifestyle, including diet, alcohol consumption, and smoking, as well as age and infections (viral or bacterial). Genetic and metabolic alterations such as obesity, gestational diabetes mellitus (GDM), and thyroidism alter epigenetic mechanisms, thereby contributing to neurodevelopmental disorders (NDs) such as embryonic neural tube defects (NTDs), autism, Down's syndrome, Rett syndrome, and later onset of neuropsychological deficits...
May 24, 2017: Genes
https://www.readbyqxmd.com/read/28537683/epigenetic-changes-of-histone-deacetylation-in-murine-oocytes-matured-in-vitro-versus-in-vivo
#11
J Huang, C-H Ding, Z-Y Li, X-B Zhang, Z-S You, C-Q Zhou, Y-W Xu
OBJECTIVE: In this study, we studied changes in histone acetylation during mouse oocytes meiosis. The aim was to investigate HDAC1 expression patterns in the mouse oocytes and effects of in-vitro maturation on epigenetic modifications during meiosis. MATERIALS AND METHODS: Immature and mature oocytes were collected from female Kunming white mice of 4-6 weeks in age. Dynamic changes of histone H3K9, H4K12 acetylation were explored. HDAC1 spatial and temporal expression patterns during meiosis and their expression changes in in-vitro maturation were determined...
May 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28537572/understanding-nucleosome-dynamics-and-their-links-to-gene-expression-and-dna-replication
#12
REVIEW
William K M Lai, B Franklin Pugh
Advances in genomics technology have provided the means to probe myriad chromatin interactions at unprecedented spatial and temporal resolution. This has led to a profound understanding of nucleosome organization within the genome, revealing that nucleosomes are highly dynamic. Nucleosome dynamics are governed by a complex interplay of histone composition, histone post-translational modifications, nucleosome occupancy and positioning within chromatin, which are influenced by numerous regulatory factors, including general regulatory factors, chromatin remodellers, chaperones and polymerases...
May 24, 2017: Nature Reviews. Molecular Cell Biology
https://www.readbyqxmd.com/read/28535770/emerging-roles-of-chromatin-in-the-maintenance-of-genome-organization-and-function-in-plants
#13
REVIEW
Zaida Vergara, Crisanto Gutierrez
Chromatin is not a uniform macromolecular entity; it contains different domains characterized by complex signatures of DNA and histone modifications. Such domains are organized both at a linear scale along the genome and spatially within the nucleus. We discuss recent discoveries regarding mechanisms that establish boundaries between chromatin states and nuclear territories. Chromatin organization is crucial for genome replication, transcriptional silencing, and DNA repair and recombination. The replication machinery is relevant for the maintenance of chromatin states, influencing DNA replication origin specification and accessibility...
May 23, 2017: Genome Biology
https://www.readbyqxmd.com/read/28535256/epigenetic-and-genetic-contributions-to-adaptation-in-chlamydomonas
#14
Ilkka Kronholm, Andrew Bassett, David Baulcombe, Sinéad Collins
Epigenetic modifications, such as DNA methylation or histone modifications, can be transmitted between cellular or organismal generations. However, there are no experiments measuring their role in adaptation, so here we use experimental evolution to investigate how epigenetic variation can contribute to adaptation. We manipulated DNA methylation and histone acetylation in the unicellular green alga Chlamydomonas reinhardtii both genetically and chemically to change the amount of epigenetic variation generated or transmitted in adapting populations in three different environments (salt stress, phosphate starvation, and high CO2) for two hundred asexual generations...
May 23, 2017: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/28534629/synthetic-posttranslational-modifications-chemical-catalyst-driven-regioselective-histone-acylation-of-native-chromatin
#15
Yoshifumi Amamoto, Yuki Aoi, Nozomu Nagashima, Hiroki Suto, Daisuke Yoshidome, Yasuhiro Arimura, Akihisa Osakabe, Daiki Kato, Hitoshi Kurumizaka, Shigehiro A Kawashima, Kenzo Yamatsugu, Motomu Kanai
Posttranslational modifications (PTMs) of histones play an important role in the complex regulatory mechanisms governing gene transcription, and their dysregulation can cause diseases such as cancer. The lack of methods for site-selectively modifying native chromatin, however, limits our understanding of the functional roles of a specific histone PTM, not as a single mark, but in the intertwined PTM network. Here, we report a synthetic catalyst DMAP-SH (DSH), which activates chemically stable thioesters (including acetyl-CoA) under physiological conditions and transfers various acyl groups to the proximate amino groups...
May 23, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28534506/lsd1-demethylates-hif1%C3%AE-to-inhibit-hydroxylation-and-ubiquitin-mediated-degradation-in-tumor-angiogenesis
#16
J-Y Lee, J-H Park, H-J Choi, H-Y Won, H-S Joo, D-H Shin, M K Park, B Han, K P Kim, T J Lee, C M Croce, G Kong
Lysine-specific demethylase 1 (LSD1), which has been considered as a potential therapeutic target in human cancer, has been known to regulate many biological functions through its non-histone substrates. Although LSD1-induced hypoxia-inducible factor alpha (HIF1α) demethylation has recently been proposed, the effect of LSD1 on the relationship between HIF1α post-translational modifications (PTMs) and HIF1α-induced tumor angiogenesis remains to be elucidated. Here, we identify a new methylation site of the HIF1α protein antagonized by LSD1 and the interplay between HIF1α protein methylation and other PTMs in regulating tumor angiogenesis...
May 22, 2017: Oncogene
https://www.readbyqxmd.com/read/28529740/copy-number-variation-and-protein-expression-of-dot1l-in-pancreatic-adenocarcinoma-as-a-potential-drug-target
#17
Heike Loeser, Dirk Waldschmidt, Fabian Kuetting, Carina Heydt, Thomas Zander, Patrick Plum, Hakan Alakus, Reinhard Buettner, Alexander Quaas
Adenocarcinoma of the pancreas has a poor prognosis. At present, no relevant personalized targets have been identified. Sequencing studies have implicated gene alterations of disruptor of telomeric silencing 1 like histone lysine methyltransferase (DOT1L) in pancreatic adenocarcinoma. DOT1L is part of the histone modification system and catalyzes methylation of H3K79, which is crucial in cell signaling and DNA damage repair. DOT1L is considered to be a target of therapy in mixed lineage leukemia gene-deficient leukemia cases and a potential target in breast carcinoma...
May 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28529604/dicer1-regulates-endometrial-carcinoma-invasion-via-histone-acetylation-and-methylation
#18
Bilan Li, Wen Lu, Junjie Qu, Yongli Zhang, Xiaoping Wan
Endometrial carcinoma (EC) is one of the most common gynecologic malignancy, but molecular mechanisms of the development and progression of EC remain unclear. Here we showed that the expression of DICER1 was negatively associated with the level of histone methylation, histone acetylation and PRC2 components SUZ12 and EZH2 in EC cells. In addition, knockdown of DICER1 significantly downregulated miR-200b and let-7i, which may then regulate their targets SUZ12 and EZH2. Furthermore, knockdown of DICER1 remarkably suppressed the expression of epithelial cell marker E-cadherin, induced the expression of mesenchymal cell marker Vimentin, and promoted the invasion of EC cells...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28529595/rnf2-knockdown-reduces-cell-viability-and-promotes-cell-cycle-arrest-in-gastric-cancer-cells
#19
Jingfang Zhang, Zhenni Sun, Yafei Han, Ruyong Yao, Lu Yue, Yan Xu, Jisheng Zhang
Rnf2 is a fundamental component of the polycomb repressive complex 1and acts as the really interesting new gene finger E3 ligase, which is responsible for histone 2A modification. Previous studies have shown that the ring finger protein 2 (Rnf2) is overexpressed in various types of tumor and has a close association with tumor development. However, few studies have been carried out into the expression and biological function of Rnf2 in gastric cancer cells. The present study measured the expression of Rnf2 in gastric cancer cells and normal epithelial gastric cells...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28529451/role-of-epigenetics-in-uveal-melanoma
#20
REVIEW
Yongyun Li, Renbing Jia, Shengfang Ge
Uveal melanoma (UM) is a severe human malignancy with a high mortality rate that demands continued research into new and alternative forms of prevention and treatment. The emerging field of epigenetics is beginning to unfold an era of contemporary approaches to reducing the risk and improving the clinical treatment of UM. Epigenetic changes have a high prevalence rate in cancer, are reversible in nature, and can lead to cancer characteristics even in mutation-free cells. The information contained in this review highlights and expands on the main mechanisms of epigenetic dysregulation in UM tumorigenesis, progression and metastasis, including microRNA expression, hypermethylation of genes and histone modification...
2017: International Journal of Biological Sciences
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