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Methylation promoter

Masashi Nomura, Kuniaki Saito, Koki Aihara, Genta Nagae, Shogo Yamamoto, Kenji Tatsuno, Hiroki Ueda, Shiro Fukuda, Takayoshi Umeda, Shota Tanaka, Shunsaku Takayanagi, Ryohei Otani, Takahide Nejo, Taijun Hana, Satoshi Takahashi, Yosuke Kitagawa, Mayu Omata, Fumi Higuchi, Taishi Nakamura, Yoshihiro Muragaki, Yoshitaka Narita, Motoo Nagane, Ryo Nishikawa, Keisuke Ueki, Nobuhito Saito, Hiroyuki Aburatani, Akitake Mukasa
To elucidate the mechanisms of malignant progression of lower-grade glioma, molecular profiling using methylation array, whole-exome sequencing, and RNA sequencing was performed for 122, 36 and 31 gliomas, respectively. This cohort included 24 matched pairs of initial lower-grade gliomas and recurrent tumors, most of which showed malignant progression. Nearly half of IDH-mutant glioblastomas that had progressed from lower-grade gliomas exhibited characteristic partial DNA demethylation in previously methylated genomic regions of their corresponding initial tumors, which had the glioma CpG island methylator phenotype (G-CIMP)...
February 13, 2019: Scientific Reports
Rajni Kant, Chia-Hung Yen, Jung-Hsien Hung, Chung-Kuang Lu, Chien-Yi Tung, Pei-Ching Chang, Yueh-Hao Chen, Yu-Chang Tyan, Yi-Ming Arthur Chen
Glycine-N-methyl transferase (GNMT) a tumor suppressor for hepatocellular carcinoma (HCC) plays a crucial role in liver homeostasis. Its expression is downregulated in almost all the tumor tissues of HCC while the mechanism of this downregulation is not yet fully understood. Recently, we identified 1,2,3,4,6-penta-O-galloyl-beta-D-glucopyranoside (PGG) as a GNMT promoter enhancer compound in HCC. In this study, we aimed to delineate the mechanism by which PGG enhances GNMT expression and to investigate its effect on GNMT suppression in HCC...
February 13, 2019: Scientific Reports
Ashot Papikian, Wanlu Liu, Javier Gallego-Bartolomé, Steven E Jacobsen
Understanding genomic functions requires site-specific manipulation of loci via efficient protein effector targeting systems. However, few approaches for targeted manipulation of the epigenome are available in plants. Here, we adapt the dCas9-SunTag system to engineer targeted gene activation and DNA methylation in Arabidopsis. We demonstrate that a dCas9-SunTag system utilizing the transcriptional activator VP64 drives robust and specific activation of several loci, including protein coding genes and transposable elements, in diverse chromatin contexts...
February 13, 2019: Nature Communications
Songxiao Zhong, Yifeng Xu, Chaoyi Yu, Xiaotuo Zhang, Lei Li, Haoran Ge, Guodong Ren, Yingxiang Wang, Jinbiao Ma, Yun Zheng, Binglian Zheng
During RNA-directed DNA methylation (RdDM), the DDR complex, composed of DRD1, DMS3, and RDM1, is responsible for recruiting DNA polymerase V (Pol V) to silence transposable elements (TEs) in plants. However, how the DDR complex is regulated remains unexplored. Here, we show that the anaphase-promoting complex/cyclosome (APC/C) regulates the assembly of the DDR complex by targeting DMS3 for degradation. We found that a substantial set of RdDM loci was commonly de-repressed in apc/c and pol v mutants, and that the defects in RdDM activity resulted from up-regulated DMS3 protein levels, which finally caused reduced Pol V recruitment...
February 13, 2019: Proceedings of the National Academy of Sciences of the United States of America
Nahyeon Kang, Su Yeon Choi, Bit Na Kim, Chang Dong Yeo, Chan Kwon Park, Young Kyoon Kim, Tae-Jung Kim, Seong-Beom Lee, Sug Hyung Lee, Jong Y Park, Mi Sun Park, Hyeon Woo Yim, Seung Joon Kim
BACKGROUND: A hypoxic microenvironment leads to an increase in the invasiveness and the metastatic potential of cancer cells within tumors via the epithelial-mesenchymal transition (EMT) and cancer stemness acquisition. However, hypoxia-induced changes in the expression and function of candidate stem cell markers and their possible molecular mechanism is still not understood. METHODS: Lung cell lines were analyzed in normoxic or hypoxic conditions. For screening among the stem cell markers, a transcriptome analysis using next-generation sequencing was performed...
February 13, 2019: BMC Cancer
Roshan Kumar Singh, Shweta Shweta, Mehanathan Muthamilarasan, Rekha Rani, Manoj Prasad
Aquaporins are versatile proteins involved in several biological as well as molecular functions, and they have been extensively studied in various plant systems. Increasing evidences indicate their role in biotic and abiotic stresses, and therefore, studying these proteins in a naturally stress-tolerant crop would provide further insights into the roles of this important protein family. Given this, the present study was performed in foxtail millet (Setaria italica), a model plant for studying biofuel, stress tolerance, and C4 photosynthetic traits...
February 13, 2019: Functional & Integrative Genomics
Katie Storey, Kevin Leder, Andrea Hawkins-Daarud, Kristin Swanson, Atique U Ahmed, Russell C Rockne, Jasmine Foo
Tumor recurrence in glioblastoma multiforme (GBM) is often attributed to acquired resistance to the standard chemotherapeutic agent, temozolomide (TMZ). Promoter methylation of the DNA repair gene MGMT (O6 -methylguanine-DNA methyltransferase) has been associated with sensitivity to TMZ, whereas increased expression of MGMT has been associated with TMZ resistance. Clinical studies have observed a downward shift in MGMT methylation percentage from primary to recurrent stage tumors; however, the evolutionary processes that drive this shift and more generally the emergence and growth of TMZ-resistant tumor subpopulations are still poorly understood...
February 2019: JCO Clinical Cancer Informatics
Yan Xu, Xiaotian Qi, Pengfei Zheng, Carlo C Berti, Peng Liu, Guangbin Dong
Carbon-hydrogen (C-H) and carbon-carbon (C-C) bonds are the main constituents of organic matter. The recent advancement of C-H functionalization technology has vastly expanded our toolbox for organic synthesis1 . In contrast, C-C activation methods that allow editing of the molecular skeleton remain limited2- . So far, a number of methods have appeared for catalytic C-C activation, particularly with ketone substrates, which are typically promoted either by ring-strain release as a thermodynamic driving force4,6 or using directing groups5,7 to control the reaction outcome...
January 30, 2019: Nature
Mikael Rydén, Paul Petrus, Daniel P Andersson, Gema Medina-Gómez, Elia Escasany, Patricia Corrales Cordón, Ingrid Dahlman, Agné Kulyté, Peter Arner
OBJECTIVE: Many overweight/obese subjects appear metabolically healthy with normal in vivo insulin sensitivity. Still, they have increased long-term risk of developing type 2 diabetes. We hypothesized that adipose tissue dysfunction involving decreased insulin action in adipocytes is present in apparently healthy overweight/obese subjects. DESIGN/METHODS: Subjects with normal metabolic health according to Adult Treatment Panel-III or Framingham risk score criteria were subdivided into 67 lean, 32 overweight and 37 obese according to body mass index...
February 13, 2019: Journal of Internal Medicine
Jiqian Xu, Hong-Bin Li, Lin Chen, Ya-Xin Wang, Shengzhong Lu, Sheng-Nan Li, Shu-Nan Cui, Hai-Rong Xiao, Lu Qin, Houxiang Hu, Shanglong Yao, You Shang
The timely resolution of pulmonary inflammation coordinated by endogenous pro-resolving mediators helps limit lung tissue injury, but few endogenous pro-resolving mediators that are normally operative during acute inflammation. The protective effects of BML-111 (5(S)-6(R)-7-trihydroxyheptanoic acid methyl ester), a potent commercially available anti-inflammatory and pro-resolving mediator, on ventilation-induced lung injury (VILI) have been extensively studied, but its characteristics as a pro-resolving mediator have not...
February 8, 2019: International Immunopharmacology
C B Item, A Schanzer, T Metz, S Greber-Platzer, J Lischka
OBJECTIVES: Elevated levels of metabolites such as ammonia and propionylcarnitine in propionic acidemia (PA) lead to an increased reactive oxygen species (ROS) production which could activate and stabilize the epigenetic regulated hypoxia-inducible factor-1α (HIF-1α). In order to evaluate the DNA methylation status of the HIF-1α binding site in PA, we investigated the antioxidant gluthatione peroxidase 3 gene (GPX3) promoter region. DESIGN AND METHODS: Using leukocyte DNA extracted from bloodspots collected 2-4 days after birth from diet free newborns, the cytosine phosphodiester bond guanine (CpG) dinucleotides of a HIF-1α binding site (CGTTTTTTACG) in the promoter region of GPX3 was retrospectively analysed...
February 9, 2019: Clinical Biochemistry
Yong Tao, Byunghak Kang, Daniel A Petkovich, Yuba R Bhandari, Julie In, Genevieve Stein-O'Brien, Xiangqian Kong, Wenbing Xie, Nicholas Zachos, Shinji Maegawa, Himani Vaidya, Stephen Brown, Ray-Whay Chiu Yen, Xiaojian Shao, Jai Thakor, Zhihao Lu, Yi Cai, Yuezheng Zhang, Izaskun Mallona, Miguel Angel Peinado, Cynthia A Zahnow, Nita Ahuja, Elana Fertig, Jean-Pierre Issa, Stephen B Baylin, Hariharan Easwaran
We addressed the precursor role of aging-like spontaneous promoter DNA hypermethylation in initiating tumorigenesis. Using mouse colon-derived organoids, we show that promoter hypermethylation spontaneously arises in cells mimicking the human aging-like phenotype. The silenced genes activate the Wnt pathway, causing a stem-like state and differentiation defects. These changes render aged organoids profoundly more sensitive than young ones to transformation by BrafV600E , producing the typical human proximal BRAFV600E -driven colon adenocarcinomas characterized by extensive, abnormal gene-promoter CpG-island methylation, or the methylator phenotype (CIMP)...
February 11, 2019: Cancer Cell
Ksenia Skvortsova, Etienne Masle-Farquhar, Phuc-Loi Luu, Jenny Z Song, Wenjia Qu, Elena Zotenko, Cathryn M Gould, Qian Du, Timothy J Peters, Yolanda Colino-Sanguino, Ruth Pidsley, Shalima S Nair, Amanda Khoury, Grady C Smith, Lisa A Miosge, Joanne H Reed, James G Kench, Mark A Rubin, Lisa Horvath, Ozren Bogdanovic, Sue Mei Lim, Jose M Polo, Christopher C Goodnow, Clare Stirzaker, Susan J Clark
Promoter CpG islands are typically unmethylated in normal cells, but in cancer a proportion are subject to hypermethylation. Using methylome sequencing we identified CpG islands that display partial methylation encroachment across the 5' or 3' CpG island borders. CpG island methylation encroachment is widespread in prostate and breast cancer and commonly associates with gene suppression. We show that the pattern of H3K4me1 at CpG island borders in normal cells predicts the different modes of cancer CpG island hypermethylation...
February 11, 2019: Cancer Cell
Carolyn M Mitchell, Jonathan J Hirst, Murray D Mitchell, Henry G Murray, Tamas Zakar
Inflammatory genes are expressed increasingly in the fetal membranes at late gestation triggering birth. Here we have examined whether epigenetic histone modifications contribute to the upregulation of proinflammatory genes in the amnion in late pregnancy and at labour. Amnion samples were collected from early pregnancy, at term in the absence of labour and after spontaneous birth. The expression of the labour-associated proinflammatory genes PTGS2, BMP2 and NAMPT was determined by reverse transcription-coupled quantitative real-time PCR (qRT-PCR)...
February 12, 2019: Molecular Human Reproduction
Jordi Martorell-Marugán, Víctor González-Rumayor, Pedro Carmona-Sáez
Motivation: The identification of differentially methylated regions (DMRs) among phenotypes is one of the main goals of epigenetic analysis. Although there are several methods developed to detect DMRs, most of them are focused on detecting relatively large differences in methylation levels and fail to detect moderate, but consistent, methylation changes that might be associated to complex disorders. Results: We present mCSEA, an R package that implements a Gene Set Enrichment Analysis method to identify differentially methylated regions from Illumina450K and EPIC array data...
February 12, 2019: Bioinformatics
Malay K Sannigrahi, Cheerneni S Srinivas, Nilesh Deokate, Sabyasachi Rakshit
Cadherin-23 (Cdh23), a long chain non-classical cadherin, exhibits strong homophilic and heterophilic binding. The physiological relevance of strong heterophilic binding with protocadherin-15 at neuroepithelial tip links is well-studied. However, the role of Cdh23 homodimers in physiology is less understood, despite its widespread expression at the cell-boundaries of various human and mouse tissues, including kidney, muscle, testes, and heart. Here, we performed immunofluorescence studies that revealed that Cdh23 is present as distinct puncta at the cell-cell boundaries of cancer cells...
February 12, 2019: Molecular Oncology
Paige M Garber, Christopher A Droege, Kristen E Carter, Nicole J Harger, Eric W Mueller
OBJECTIVE: Ketamine is an N-methyl-D-aspartate (NMDA) antagonist with emerging evidence assessing its use as a continuous infusion agent to provide concomitant analgesia and sedation. The role of ketamine as adjunctive therapy in mechanically ventilated patients is unclear. This study sought to investigate the impact of adjunctive continuous infusion ketamine on concomitant analgesic and sedative dosing while providing goal comfort in mechanically ventilated patients. METHODS: This retrospective, two-center, intrapatient comparison study included mechanically ventilated, adult ICU patients who received continuous infusion ketamine with at least one other analgesic or sedative infusion...
February 11, 2019: Pharmacotherapy
Pengyu Jing, Nianlin Xie, Ximing Zhu, Haizhou Dang, Zhongping Gu
Arginine methylation as a common pattern of post-translational modification is involved in many cellular biological processes. Protein arginine methyltransferase 5 (PRMT5) is a primary enzyme in charge of symmetric dimethylation (me2s) of arginine residues. Increasing literatures lead to the belief that PRMT5, as a potential oncogene, plays crucial roles in the tumorigenesis and progression of cancers. First of all, PRMT5 is overexpressed in several cancer cells, with various sub-cellular localization in different type of cells and different phases...
December 2018: Journal of Thoracic Disease
Jingwen Sun, Jinjing Zhang, Yue Wang, Yan Li, Rui Zhang
Background: Epigenetic silencing of tumor suppressor genes plays important role in acute myeloid leukemia (AML). Recently, SPRED1, a negative regulator of the RAS MAPK pathway, is identified as a tumour suppressor downregulated in AML. However, little is known regarding its underlying dysregulation in AML. In this study, we investigated methylation status of SPRED1 promoters and their association with mRNA levels in AML. Methods: Methylation level were measured in four regions of SPRED1 (#1: 310 bp ~ 723 bp, #2: 810 bp ~ 1299 bp, #3: 1280 bp ~ 1742 bp and #4: 1715 bp ~ 2059 bp) in a total of 16 patients with de novonon-acute promyelocytic leukemia (non-APL) and three patients who got complete remission after induction treatment using the Sequenom MassARRAY platform...
2019: International Journal of Medical Sciences
Li Zhang, Weilin Li, Lei Cao, Jiaying Xu, Yun Qian, Huarong Chen, Yanquan Zhang, Wei Kang, Hongyan Gou, Chi Chun Wong, Jun Yu
Promoter methylation plays a vital role in tumorigenesis through transcriptional silencing of tumor suppressive genes. Using genome-wide methylation array, we first identified PBX/Knotted Homeobox 2 (PKNOX2) as a candidate tumor suppressor in gastric cancer. PKNOX2 mRNA expression is largely silenced in gastric cancer cell lines and primary gastric cancer via promoter methylation. Promoter methylation of PKNOX2 was associated with poor survival in gastric cancer patients. A series of in vitro and in vivo functional studies revealed that PKNOX2 functions as a tumor suppressor...
February 11, 2019: Oncogene
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