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histone methyltransferase

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https://www.readbyqxmd.com/read/29783122/bix-01294-promotes-the-differentiation-of-adipose-mesenchymal-stem-cells-into-adipocytes-and-neural-cells-in-arbas-cashmere-goats
#1
Qing Wang, Xiao Wang, Defang Lai, Jin Deng, Zhuang Hou, Hao Liang, Dongjun Liu
Chromatin remodeling plays an essential role in regulating gene transcription. BIX-01294 is a specific inhibitor of histone methyltransferase G9a, which is responsible for methylation of histone H3 lysine 9 (H3K9) that can also regulate DNA methylation and chromatin remodeling. The purpose of this study was to investigate the effects of BIX-01294 on the potential of goat adipose derived stem cells (gADSCs) to differentiate into adipocytes and neural cells. To accomplish this, BIX-01294 was used to treat gADSCs for 24 h, and the global level of DNA methylation as well as the expression of genes related to cell proliferation, apoptosis and pluripotency were detected...
May 14, 2018: Research in Veterinary Science
https://www.readbyqxmd.com/read/29782530/histone-methylation-changes-are-required-for-life-cycle-progression-in-the-human-parasite-schistosoma-mansoni
#2
David Roquis, Aaron Taudt, Kathrin K Geyer, Gilda Padalino, Karl F Hoffmann, Nancy Holroyd, Matt Berriman, Benoît Aliaga, Cristian Chaparro, Christoph Grunau, Ronaldo de Carvalho Augusto
Epigenetic mechanisms and chromatin structure play an important role in development. Their impact is therefore expected to be strong in parasites with complex life cycles and multiple, strikingly different, developmental stages, i.e. developmental plasticity. Some studies have already described how the chromatin structure, through histone modifications, varies from a developmental stage to another in a few unicellular parasites. However, this, to our knowledge, has never been done before in multicellular metazoan parasites...
May 21, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29779941/the-epigenetic-state-of-prdm16-regulated-enhancers-in-radial-glia-controls-cortical-neuron-position
#3
José-Manuel Baizabal, Meeta Mistry, Miguel Turrero García, Nicolás Gómez, Olubusola Olukoya, Diana Tran, Matthew B Johnson, Christopher A Walsh, Corey C Harwell
The epigenetic landscape is dynamically remodeled during neurogenesis. However, it is not understood how chromatin modifications in neural stem cells instruct the formation of complex structures in the brain. We report that the histone methyltransferase PRDM16 is required in radial glia to regulate lineage-autonomous and stage-specific gene expression programs that control number and position of upper layer cortical projection neurons. PRDM16 regulates the epigenetic state of transcriptional enhancers to activate genes involved in intermediate progenitor cell production and repress genes involved in cell migration...
May 15, 2018: Neuron
https://www.readbyqxmd.com/read/29775417/targeting-histone-methyltransferase-enhancer-of-zeste-homolog-2-inhibits-renal-epithelial-mesenchymal-transition-and-attenuates-renal-fibrosis
#4
Xiaoxu Zhou, Chongxiang Xiong, Evelyn Tolbert, Ting C Zhao, George Bayliss, Shougang Zhuang
Enhancer of zeste homolog-2 (EZH2) is a methyltransferase that induces histone H3 lysine 27 trimethylation (H3K27me3) and functions as an oncogenic factor in many cancer types. Its role in renal epithelial-mesenchymal transition (EMT) remains unknown. In this study, we found that EZH2 and H3K27me3 were highly expressed in mouse kidney with unilateral ureteral obstruction and cultured mouse kidney proximal tubular (TKPT) cells undergoing EMT. Inhibition of EZH2 with 3-deazaneplanocin A (3-DZNeP) attenuated renal fibrosis, which was associated with preserving E-cadherin expression and inhibiting Vimentin up-regulation in the obstructed kidney...
May 18, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29774127/paf1-complex-interactions-with-setdb1-mediate-promoter-h3k9-methylation-and-transcriptional-repression-of-hoxa9-and-meis1-in-acute-myeloid-leukemia
#5
James Ropa, Nirmalya Saha, Zhiling Chen, Justin Serio, Wei Chen, Dattatreya Mellacheruvu, Lili Zhao, Venkatesha Basrur, Alexey I Nesvizhskii, Andrew G Muntean
The Polymerase Associated Factor 1 complex (PAF1c) is an epigenetic co-modifying complex that directly contacts RNA polymerase II (RNAPII) and several epigenetic regulating proteins. Mutations, overexpression and loss of expression of subunits of the PAF1c are observed in various forms of cancer suggesting proper regulation is needed for cellular development. However, the biochemical interactions with the PAF1c that allow dynamic gene regulation are unclear. We and others have shown that the PAF1c makes a direct interaction with MLL fusion proteins, which are potent oncogenic drivers of acute myeloid leukemia (AML)...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29774113/ezh2-inhibitors-sensitize-myeloma-cell-lines-to-panobinostat-resulting-in-unique-combinatorial-transcriptomic-changes
#6
Taylor Harding, Jessica Swanson, Brian Van Ness
Multiple myeloma (MM) remains a largely incurable hematologic cancer due to an inability to broadly target inevitable drug-resistant relapse. Epigenetic abnormalities are abundantly present in multiple myeloma and have increasingly demonstrated critical roles for tumor development and relapse to standard therapies. Accumulating evidence suggests that the histone methyltransferase EZH2 is aberrantly active in MM. We tested the efficacy of EZH2 specific inhibitors in a large panel of human MM cell lines (HMCLs) and found that only a subset of HMCLs demonstrate single agent sensitivity despite ubiquitous global H3K27 demethylation...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29773653/inhibition-of-protein-arginine-methyltransferase-5-enhances-hepatic-mitochondrial-biogenesis
#7
Lei Huang, Jehnan Liu, Xiao-Ou Zhang, Katelyn Sibley, Sonia M Najjar, Mary M Lee, Joae Qiong Wu
Protein arginine methyltransferase 5 (PRMT5) regulates gene expression either transcriptionallyly by symmetric dimethylation of arginine residues on histones H4R3, H3R8 and H2AR3, or at the post-translational level by methylation of non-histone target proteins. While emerging evidence suggests that PRMT5 functions as an oncogene, its role in metabolic diseases is not well defined. We investigated the role of PRMT5 in promoting high fat-induced hepatic steatosis. High fat diet up-regulated PRMT5 levels in the liver, but not in other metabolically relevant tissues such as skeletal muscle or white and brown adipose tissue...
May 17, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29765857/dna-methylation-and-adult-neurogenesis
#8
REVIEW
Emily M Jobe, Xinyu Zhao
The role of DNA methylation in brain development is an intense area of research because the brain has particularly high levels of CpG and mutations in many of the proteins involved in the establishment, maintenance, interpretation, and removal of DNA methylation impact brain development and/or function. These include DNA methyltransferase (DNMT), Ten-Eleven Translocation (TET), and Methyl-CpG binding proteins (MBPs). Recent advances in sequencing breadth and depth as well the detection of different forms of methylation have greatly expanded our understanding of the diversity of DNA methylation in the brain...
November 9, 2017: Brain Plasticity
https://www.readbyqxmd.com/read/29765028/dot1l-inhibition-attenuates-graft-versus-host-disease-by-allogeneic-t-cells-in-adoptive-immunotherapy-models
#9
Yuki Kagoya, Munehide Nakatsugawa, Kayoko Saso, Tingxi Guo, Mark Anczurowski, Chung-Hsi Wang, Marcus O Butler, Cheryl H Arrowsmith, Naoto Hirano
Adoptive T-cell therapy is a promising therapeutic approach for cancer patients. The use of allogeneic T-cell grafts will improve its applicability and versatility provided that inherent allogeneic responses are controlled. T-cell activation is finely regulated by multiple signaling molecules that are transcriptionally controlled by epigenetic mechanisms. Here we report that inhibiting DOT1L, a histone H3-lysine 79 methyltransferase, alleviates allogeneic T-cell responses. DOT1L inhibition reduces miR-181a expression, which in turn increases the ERK phosphatase DUSP6 expression and selectively ameliorates low-avidity T-cell responses through globally suppressing T-cell activation-induced gene expression alterations...
May 15, 2018: Nature Communications
https://www.readbyqxmd.com/read/29764959/a-targeted-rnai-screen-reveals-drosophila-female-sterile-genes-that-control-the-size-of-germline-stem-cell-niche-during-development
#10
Yueh Cho, Chun-Ming Lai, Kun-Yang Lin, Hwei-Jan Hsu
Adult stem cells maintain tissue homeostasis. This unique capability largely depends on the stem cell niche, a specialized microenvironment, which preserves stem cell identity through physical contacts and secreted factors. In many cancers, latent tumor cell niches are thought to house stem cells and aid tumor initiation. However, in developing tissue and cancer it is unclear how the niche is established. The well-characterized germline stem cells (GSCs) and niches in the Drosophila melanogaster ovary provide an excellent model to address this fundamental issue...
May 15, 2018: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/29763912/-a-succinate-ether-derivative-of-tocotrienol-enhances-dickkopf-1-gene-expression-through-epigenetic-alterations-in-malignant-mesothelioma-cells
#11
Ayami Sato, Haruka Ueno, Momoka Fusegi, Saki Kaneko, Kakeru Kohno, Nantiga Virgona, Akira Ando, Yuko Sekine, Tomohiro Yano
BACKGROUND: Wnt signaling plays an essential role in tumor cell growth, including the development of malignant mesothelioma (MM). Epigenetic silencing of negative Wnt regulators leading to constitutive Wnt signaling has been observed in various cancers and warrants further attention. We have reported that a succinate ether derivative of α-tocotrienol (T3E) has potent cytotoxic effects in MM cells. Thus, in this study, we investigated whether the anti-MM effect of T3E could be mediated via the epigenetic alteration of the Wnt antagonist gene, Dickkopf-1 (DKK1)...
May 15, 2018: Pharmacology
https://www.readbyqxmd.com/read/29762619/isolation-and-genome-sequencing-of-individual-circulating-tumor-cells-using-hydrogel-encapsulation-and-laser-capture-microdissection
#12
Emily S Park, Justin P Yan, Richard A Ang, Jeong Hyun Lee, Xiaoyan Deng, Simon P Duffy, Kevin Beja, Matti Annala, Peter C Black, Kim N Chi, Alexander W Wyatt, Hongshen Ma
Circulating tumor cells (CTCs) are malignant cells released into the bloodstream with the potential to form metastases in secondary sites. These cells, acquired non-invasively, represent a sample of highly relevant tumor tissue that is an alternative to difficult and low-yield tumor biopsies. In recent years, there has been growing interest in genomic profiling of CTCs to enable longitudinal monitoring of the tumor's adaptive response to therapy. However, due to their extreme rarity, genotyping CTCs has proved challenging...
May 15, 2018: Lab on a Chip
https://www.readbyqxmd.com/read/29755682/evaluation-of-the-impact-of-s-adenosylmethionine-dependent-methyltransferase-inhibitor-3-deazaneplanocin-a-on-tissue-injury-and-cognitive-function-in-mice
#13
Eva Lhuissier, Juliette Aury-Landas, Valentine Bouet, Céline Bazille, Yohann Repesse, Thomas Freret, Karim Boumédiene, Catherine Baugé
Cancer patients display cognitive impairment due, at least partly, to the treatments. Additionally, chemotherapeutic treatments can lead to organ injury, limiting their use, and are likely to have negative impacts on patients' quality of life. The aim of this study was to investigate the toxicity of 3-Deazaneplanocin A (DZNep) on several tissues and organs, as well as on cognitive functions. DZNep is an inhibitor of S-adenosylmethionine-dependent methyltransferase (in particular of the histone methyltransferase EZH2) which showed antitumoral functions in preclinical trials but whose effects on behavior and on organs (side effects) are not known...
April 17, 2018: Oncotarget
https://www.readbyqxmd.com/read/29753921/de-novo-loss-of-function-variants-of-ash1l-are-associated-with-an-emergent-neurodevelopmental-disorder
#14
Wei Shen, Patti Krautscheid, Audrey M Rutz, Pinar Bayrak-Toydemir, Sarah L Dugan
De novo variants of ASH1L, which encodes a histone methyltransferase, have been reported in a few patients with intellectual disability and autistic features. Here, we identified a novel de novo frame-shift variant, c.2422_2423delAAinsT which predicts p.(Lys808TyrfsTer40), in ASH1L in a patient with multiple congenital anomalies (MCA), fine motor developmental delay, learning difficulties, attention deficit hyperactivity disorder, sleep apnea, and scoliosis. This frame-shift variant is expected to result in loss-of-function...
May 10, 2018: European Journal of Medical Genetics
https://www.readbyqxmd.com/read/29750576/suv39h1-dnmt3a-dependent-methylation-of-the-rb1-promoter-stimulates-pin1-expression-and-melanoma-development
#15
Garam Kim, Jin-Young Kim, Sung-Chul Lim, Kwang Youl Lee, Okyun Kim, Hong Seok Choi
Melanoma is among the most aggressive and treatment-resistant human cancers. Aberrant histone H3 methylation at Lys 9 (H3K9) correlates with carcinogenic gene silencing, but the significance of suppressor of variegation 3-9 homolog 1 (SUV39H1), an H3K9-specific methyltransferase, in melanoma initiation and progression remains unclear. Here, we show that SUV39H1-mediated H3K9 trimethylation facilitates retinoblastoma ( RB) 1 promoter CpG island methylation by interacting with DNA methyltransferase 3A and decreasing RB mRNA and protein in melanoma cells...
May 11, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29746925/smyd3-controls-a-wnt-responsive-epigenetic-switch-for-ascl2-activation-and-cancer-stem-cell-maintenance
#16
Tao Wang, Hong Wu, Sha Liu, Zengjie Lei, Zhongyi Qin, Liangzhi Wen, Kai-Jun Liu, Xing-Wei Wang, Yan Guo, Qin Liu, Lei Liu, Jun Wang, Li Lin, Chengyi Mao, Xiangfeng Zhu, Hualiang Xiao, Xiuwu Bian, Dongfeng Chen, Chuan Xu, Bin Wang
Tumor growth is fueled by subset of cells with stem cell properties (Cancer stem cells, CSCs). While persistent activation of Wnt/β-catenin signaling confers CSC properties, it remains unclear how epigenetic modifications regulate Wnt target genes to dictate their self-renewal. Here, we report a novel Wnt-responsive epigenetic switch for CSC maintenance through activating the stem cell transcription factor ASCL2 in gastric carcinoma (GC). We characterize ASCL2-expressing (ASCL2+ ) GC cells as a subset of Wnt-responsive CSCs that depend on ASCL2 for self-renewal...
May 7, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29743234/the-ribosome-a-hot-spot-for-the-identification-of-new-types-of-protein-methyltransferases
#17
Steven G Clarke
Cellular physiology depends on the alteration of protein structures by covalent modification reactions.  Using a combination of bioinformatic, genetic, biochemical, and mass spectrometric approaches, it has been possible to probe ribosomal proteins from the yeast Saccharomyces cerevisiae for posttranslationally methylated amino acid residues and for the enzymes that catalyze these modifications.  These efforts have resulted in the identification and characterization of the first protein histidine methyltransferase, the first N-terminal protein methyltransferase, two unusual types of protein arginine methyltransferases, and a new type of cysteine methylation...
May 9, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29742153/identification-of-a-peptide-inhibitor-for-the-histone-methyltransferase-whsc1
#18
Michael J Morrison, P Ann Boriack-Sjodin, Kerren K Swinger, Tim J Wigle, Dipti Sadalge, Kevin W Kuntz, Margaret Porter Scott, William P Janzen, Richard Chesworth, Kenneth W Duncan, Darren M Harvey, John W Lampe, Lorna H Mitchell, Robert A Copeland
WHSC1 is a histone methyltransferase that is responsible for mono- and dimethylation of lysine 36 on histone H3 and has been implicated as a driver in a variety of hematological and solid tumors. Currently, there is a complete lack of validated chemical matter for this important drug discovery target. Herein we report on the first fully validated WHSC1 inhibitor, PTD2, a norleucine-containing peptide derived from the histone H4 sequence. This peptide exhibits micromolar affinity towards WHSC1 in biochemical and biophysical assays...
2018: PloS One
https://www.readbyqxmd.com/read/29741722/prenatal-exposure-to-bisphenol-a-analogues-on-male-reproductive-functions-in-mice
#19
Mingxin Shi, Nikola Sekulovski, James A MacLean, Kanako Hayashi
This study was performed to examine whether prenatal exposure to bisphenol (BP) A analogues, BPE and BPS, negatively impacts male reproductive functions and testis development using mice as a model. CD-1 mice were orally exposed to control treatment (corn oil), BPA, BPE, and BPS (0.5, 20, or 50 µg/kg/day) from gestational day 11 (the presence of vaginal plug = 1) to birth. Although sperm counts were significantly reduced by BPA, BPE, or BPS on postnatal day (PND) 60, only BPE or BPS exposure remained low for sperm motility...
March 21, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29740169/gain-of-function-mutations-in-dnmt3a-in-patients-with-paraganglioma
#20
Laura Remacha, Maria Currás-Freixes, Raúl Torres-Ruiz, Francesca Schiavi, Rafael Torres-Pérez, Bruna Calsina, Rocío Letón, Iñaki Comino-Méndez, Juan M Roldán-Romero, Cristina Montero-Conde, María Santos, Lucía Inglada Pérez, Guillermo Pita, María R Alonso, Emiliano Honrado, Susana Pedrinaci, Benedicto Crespo-Facorro, Antonio Percesepe, Maurizio Falcioni, Sandra Rodríguez-Perales, Esther Korpershoek, Santiago Ramón-Maiques, Giuseppe Opocher, Cristina Rodríguez-Antona, Mercedes Robledo, Alberto Cascón
PURPOSE: The high percentage of patients carrying germline mutations makes pheochromocytomas/paragangliomas the most heritable of all tumors. However, there are still cases unexplained by mutations in the known genes. We aimed to identify the genetic cause of disease in patients strongly suspected of having hereditary tumors. METHODS: Whole-exome sequencing was applied to the germlines of a parent-proband trio. Genome-wide methylome analysis, RNA-seq, CRISPR/Cas9 gene editing, and targeted sequencing were also performed...
May 8, 2018: Genetics in Medicine: Official Journal of the American College of Medical Genetics
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