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https://www.readbyqxmd.com/read/28916733/clonal-expansion-and-epigenetic-reprogramming-following-deletion-or-amplification-of-mutant-idh1
#1
Tali Mazor, Charles Chesnelong, Aleksandr Pankov, Llewellyn E Jalbert, Chibo Hong, Josie Hayes, Ivan V Smirnov, Roxanne Marshall, Camila F Souza, Yaoqing Shen, Pavithra Viswanath, Houtan Noushmehr, Sabrina M Ronen, Steven J M Jones, Marco A Marra, J Gregory Cairncross, Arie Perry, Sarah J Nelson, Susan M Chang, Andrew W Bollen, Annette M Molinaro, Henrik Bengtsson, Adam B Olshen, Samuel Weiss, Joanna J Phillips, H Artee Luchman, Joseph F Costello
IDH1 mutation is the earliest genetic alteration in low-grade gliomas (LGGs), but its role in tumor recurrence is unclear. Mutant IDH1 drives overproduction of the oncometabolite d-2-hydroxyglutarate (2HG) and a CpG island (CGI) hypermethylation phenotype (G-CIMP). To investigate the role of mutant IDH1 at recurrence, we performed a longitudinal analysis of 50 IDH1 mutant LGGs. We discovered six cases with copy number alterations (CNAs) at the IDH1 locus at recurrence. Deletion or amplification of IDH1 was followed by clonal expansion and recurrence at a higher grade...
September 15, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28916632/tissue-sex-and-age-specific-dna-methylation-of-rat-glucocorticoid-receptor-gene-promoter-and-insulin-like-growth-factor-2-imprinting-control-region
#2
Ogechukwu Brenda Agba, Ludwig Lausser, Klaus Huse, Christoph Bergmeier, Niels Jahn, Marco Groth, Martin Bens, Arne Sahm, Maria Gall, Otto W Witte, Hans A Kestler, Matthias Schwab, Matthias Platzer
Tissue-, sex- and age-specific epigenetic modifications such as DNA methylation are largely unknown. Changes in DNA methylation of the glucocorticoid receptor gene (NR3C1) and imprinting control region (ICR) of IGF2 and H19 genes during the lifespan are particularly interesting since these genes are susceptible to epigenetic modifications by prenatal stress or malnutrition. They are important regulators of development and aging. Methylation changes of NR3C1 affect glucocorticoid receptor expression, which is associated with stress sensitivity and stress-related diseases predominantly occurring during aging...
September 15, 2017: Physiological Genomics
https://www.readbyqxmd.com/read/28914964/clinicopathological-and-molecular-implications-of-aberrant-ttf-1-expression-in-colorectal-carcinomas-an-immunohistochemical-analysis-of-1-319-cases-using-three-different-antibody-clones
#3
Jeong Mo Bae, Jung Ho Kim, Jeong Hwan Park, Hye Eun Park, Nam-Yun Cho, Gyeong Hoon Kang
AIMS: The precise profile of aberrant expression of thyroid transcription factor-1 (TTF-1) according to antibody clones in colorectal carcinomas (CRCs) has been controversial. Moreover, the detailed clinicopathological and molecular features of CRCs with TTF-1 expression have rarely been investigated. Here, we evaluated the TTF-1 expression status in a large series of CRC cases using three different antibody clones. METHODS AND RESULTS: Immunohistochemistry for TTF-1 using clones 8G7G3/1, SPT24, and SP141 was performed on tumour tissues of 1,319 primary CRCs and 98 corresponding metastatic lesions...
September 15, 2017: Histopathology
https://www.readbyqxmd.com/read/28912427/dna-methylation-profiling-reveals-common-signatures-of-tumorigenesis-and-defines-epigenetic-prognostic-subtypes-of-canine-diffuse-large-b-cell-lymphoma
#4
Serena Ferraresso, Arianna Aricò, Tiziana Sanavia, Silvia Da Ros, Massimo Milan, Luciano Cascione, Stefano Comazzi, Valeria Martini, Mery Giantin, Barbara Di Camillo, Sandro Mazzariol, Diana Giannuzzi, Laura Marconato, Luca Aresu
Epigenetic deregulation is a hallmark of cancer characterized by frequent acquisition of new DNA methylation in CpG islands. To gain insight into the methylation changes of canine DLBCL, we investigated the DNA methylome in primary DLBCLs in comparison with control lymph nodes by genome-wide CpG microarray. We identified 1,194 target loci showing different methylation levels in tumors compared with controls. The hypermethylated CpG loci included promoter, 5'-UTRs, upstream and exonic regions. Interestingly, targets of polycomb repressive complex in stem cells were mostly affected suggesting that DLBCL shares a stem cell-like epigenetic pattern...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28910750/analysis-of-methylation-profiling-data-of-hyperplasia-and-primary-and-metastatic-endometrial-cancers
#5
Xihai Wu, Jilan Miao, Jingyan Jiang, Fangmei Liu
OBJECTIVE: Endometrial cancer is a prevalent cancer, and its metastasis causes low survival rate. This study aims to utilize DNA methylation data to investigate the mechanism of the development and metastasis of endometrial cancer. STUDY DESIGN: Methylation profiling data were down-loaded from Gene Expression Omnibus, including 8 hyperplasias, 33 primary and 53 metastatic endometrial cancers. COHCAP package and annotation files were utilized to identify differentially methylated genes (DMGs) and CpG islands between the three different endometrial diseases...
September 1, 2017: European Journal of Obstetrics, Gynecology, and Reproductive Biology
https://www.readbyqxmd.com/read/28910327/in-silico-analysis-of-cis-acting-regulatory-elements-of-pathogenesis-related-proteins-of-arabidopsis-thaliana-and-oryza-sativa
#6
Amritpreet Kaur, Pratap Kumar Pati, Aparna Maitra Pati, Avinash Kaur Nagpal
Pathogenesis related (PR) proteins are low molecular weight family of proteins induced in plants under various biotic and abiotic stresses. They play an important role in plant-defense mechanism. PRs have wide range of functions, acting as hydrolases, peroxidases, chitinases, anti-fungal, protease inhibitors etc. In the present study, an attempt has been made to analyze promoter regions of PR1, PR2, PR5, PR9, PR10 and PR12 of Arabidopsis thaliana and Oryza sativa. Analysis of cis-element distribution revealed the functional multiplicity of PRs and provides insight into the gene regulation...
2017: PloS One
https://www.readbyqxmd.com/read/28894234/elevated-umod-methylation-level-in-peripheral-blood-is-associated-with-gout-risk
#7
Yong Yang, Xiaoying Chen, Haochang Hu, Yuting Jiang, Hang Yu, Jie Dai, Yiyi Mao, Shiwei Duan
Uromodulin (UMOD) encodes an uromodulin glycoprotein, and its mutation results in uromodulin glycoprotein dysfunction and the occurrence of gout. The aim of our study was to assess whether UMOD methylation could predict the risk of gout. A total of 89 sporadic gout cases and 103 age and gender-matched healthy controls were recruited in this study. UMOD methylation level was determined by quantitative methylation-specific PCR (qMSP) in peripheral blood, and the percentage of methylated reference (PMR) was described to represent the methylation level...
September 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28892045/mn1-overexpression-is-driven-by-loss-of-dnmt3b-methylation-activity-in-inv-16-pediatric-aml
#8
N S D Larmonie, T C J M Arentsen-Peters, A Obulkasim, D Valerio, E Sonneveld, A A Danen-van Oorschot, V de Haas, D Reinhardt, M Zimmermann, J Trka, A Baruchel, R Pieters, M M van den Heuvel-Eibrink, C M Zwaan, M Fornerod
In acute myeloid leukemia (AML), specific genomic aberrations induce aberrant methylation, thus directly influencing the transcriptional programing of leukemic cells. Therefore, therapies targeting epigenetic processes are advocated as a promising therapeutic tool for AML treatment. However, to develop new therapies, a comprehensive understanding of the mechanism(s) driving the epigenetic changes as a result of acquired genetic abnormalities is necessary. This understanding is still lacking. In this study, we performed genome-wide CpG-island methylation profiling on pediatric AML samples...
September 11, 2017: Oncogene
https://www.readbyqxmd.com/read/28889375/a-versatile-assay-for-detection-of-aberrant-dna-methylation-in-bladder-cancer
#9
Stella Tommasi, Ahmad Besaratinia
Urothelial carcinoma of the bladder is one of the most common malignancies in the industrialized world, mainly caused by smoking and occupational exposure to chemicals. The favorable prognosis of early stage bladder cancer underscores the importance of early detection for the treatment of this disease. The high recurrence rate of this malignancy also highlights the need for close post-diagnosis monitoring of bladder cancer patients. As for other malignancies, aberrant DNA methylation has been shown to play a crucial role in the initiation and progression of bladder cancer, and thus holds great promise as a diagnostic and prognostic biological marker...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28888056/comparison-of-genome-wide-analysis-techniques-to-dna-methylation-analysis-in-human-cancer
#10
REVIEW
Narges Soozangar, Mohammad Reza Sadeghi, Farhad Jeddi, Mohammad Hossein Somi, Masoud Shirmohamadi, Nasser Samadi
DNA methylation was the first epigenetic modification to be detected in human cancers with specific relation to aberrant gene expression. Herein, DNA methylation analysis explains how epigenetic patterns affect gene expression level. Hypermethylation at tumor suppressor gene loci leads to increased tumorigenesis due to tumor suppressor gene silencing, whereas global hypomethylation of CpG islands (CGIs) is followed by genomic instability and aberrant activation of multiple oncogenes. Therefore, characterization of the genes which silenced or activated epigenetically in human tumor cells can improve our understanding of cancer biology...
September 9, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28884721/-a-search-of-target-regions-for-association-studies-between-dna-methylation-and-cognitive-impairment-in-schizophrenia
#11
N V Kondratiev, M V Alfimova, V E Golimbet
AIM: To develop a strategy for the search for candidate genes and targets for epigenetic studies of cognitive impairments in patients with schizophrenia. MATERIAL AND METHODS: A search for literature on epigenetics of schizophrenia and cognitive functions was performed. Single nucleotide polymorphisms (SNPs) that can create or abolish a site for DNA methylation or transcription factor sites were determined using a custom script. RESULTS AND CONCLUSION: Eight candidate genes, including BDNF, COMT, RELN, SNRPN, PSMA4, FAM63B, IL-1RAP, MAD1L1, as well as 750 targets in CpG islands in the linkage regions identified in GWAS of schizophrenia and 406 targets in SNV located within transcription factor binding sites were selected...
2017: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
https://www.readbyqxmd.com/read/28883545/copy-number-rather-than-epigenetic-alterations-are-the-major-dictator-of-imprinted-methylation-in-tumors
#12
Alex Martin-Trujillo, Enrique Vidal, Ana Monteagudo-Sa Nchez, Marta Sanchez-Delgado, Sebastian Moran, Jose Ramon Hernandez Mora, Holger Heyn, Miriam Guitart, Manel Esteller, David Monk
It has been postulated that imprinting aberrations are common in tumors. To understand the role of imprinting in cancer, we have characterized copy-number and methylation in over 280 cancer cell lines and confirm our observations in primary tumors. Imprinted differentially methylated regions (DMRs) regulate parent-of-origin monoallelic expression of neighboring transcripts in cis. Unlike single-copy CpG islands that may be prone to hypermethylation, imprinted DMRs can either loose or gain methylation during tumorigenesis...
September 7, 2017: Nature Communications
https://www.readbyqxmd.com/read/28877467/the-set1-complex-selects-actively-transcribed-target-genes-via-multivalent-interaction-with-cpg-island-chromatin
#13
David A Brown, Vincenzo Di Cerbo, Angelika Feldmann, Jaewoo Ahn, Shinsuke Ito, Neil P Blackledge, Manabu Nakayama, Michael McClellan, Emilia Dimitrova, Anne H Turberfield, Hannah K Long, Hamish W King, Skirmantas Kriaucionis, Lothar Schermelleh, Tatiana G Kutateladze, Haruhiko Koseki, Robert J Klose
Chromatin modifications and the promoter-associated epigenome are important for the regulation of gene expression. However, the mechanisms by which chromatin-modifying complexes are targeted to the appropriate gene promoters in vertebrates and how they influence gene expression have remained poorly defined. Here, using a combination of live-cell imaging and functional genomics, we discover that the vertebrate SET1 complex is targeted to actively transcribed gene promoters through CFP1, which engages in a form of multivalent chromatin reading that involves recognition of non-methylated DNA and histone H3 lysine 4 trimethylation (H3K4me3)...
September 5, 2017: Cell Reports
https://www.readbyqxmd.com/read/28877249/silencing-of-interferon-regulatory-factor-gene-6-in-melanoma
#14
Yoshimasa Nobeyama, Hidemi Nakagawa
BACKGROUND: Methylation of a CpG island (CGI; a dense cluster of CpGs) located in the 5' region of a gene suppresses transcription of that gene. Interferon regulatory factor 6 (IRF6) is associated with the expression of interferon, which is used as an effective adjuvant therapy for melanoma, and is regarded as a tumor suppressor. However, little is known about the methylation status of the IRF6 gene in melanoma. OBJECTIVE: The purpose was to determine the methylation status of the CGI located in the 5' region of IRF6 (5' IRF6 CGI) in melanoma...
2017: PloS One
https://www.readbyqxmd.com/read/28875477/effects-of-pon1-gene-promoter-dna-methylation-and-genetic-variations-on-the-clinical-outcomes-of-dual-antiplatelet-therapy-for-patients%C3%A2-undergoing-percutaneous-coronary-intervention
#15
He-Ping Lei, Xi-Yong Yu, Hong Wu, Yan-Hong Kang, Wan-Ping Zhong, Li-Yun Cai, Meng-Zhen Zhang, Ji-Yan Chen, Li-Ping Mai, Qing-Shan Ding, Min Yang, Shi-Long Zhong
INTRODUCTION AND OBJECTIVE: The relationship between either paraoxonase 1 (PON1) gene promoter DNA methylation or genetic variations and bleeding or major adverse cardiac events after dual antiplatelet therapy has been incompletely characterized. We aimed to systematically investigate the role of genetic variations and DNA methylation of the PON1 CpG island promoter on the clinical outcomes of dual antiplatelet therapy for patients with coronary artery disease (CAD) who underwent percutaneous coronary intervention (PCI)...
September 5, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28875006/aberrant-methylation-mediated-suppression-of-apaf1-in-myelodysplastic-syndrome
#16
Farhad Zaker, Nahid Nasiri, Naser Amirizadeh, Seyed Mohsen Razavi, Marjan Yaghmaie, Ladan Teimoori-Toolabi, Ali Maleki, Masoumeh Bakhshayesh
Background: Myelodysplastic syndromes (MDSs) include a diverse group of clonal bone marrow disorders characterized by ineffective hematopoiesis and pancytopenia. It was found that down regulation of APAF1, a putative tumor suppressor gene (TSG), leads to resistance to chemotherapy and disease development in some cancers. In this study, we investigated the relation of APAF1 methylation status with its expression and clinicopathological factors in myelodysplastic syndrome (MDS) patients. Materials andMethods: Methylation Sensitive-High Resolution Melting Curve Analysis (MS-HRM) was employed in studying the methylation of CpG islands in the APAF1promoter region in MDS...
April 1, 2017: International Journal of Hematology-oncology and Stem Cell Research
https://www.readbyqxmd.com/read/28870864/counter-regulation-of-ecrg4-gene-expression-by-hypermethylation-dependent-inhibition-and-the-sp1-transcription-factor-dependent-stimulation-of-the-c2orf40-promoter
#17
Xitong Dang, Xiaorong Zeng, Raul Coimbra, Brian P Eliceiri, Andrew Baird
The human cytokine precursor ECRG4 has been associated with multiple physiological, developmental and pathophysiological processes involving cell proliferation, cell migration, innate immunity, inflammation, cancer progression and metastases. Although down-regulation of ECRG4 gene expression has been largely attributed to hypermethylation of CpG islands in the 5'untranslated region of the ECRG4 promoter, the mechanisms that underlie the dynamics of its regulation have never been systematically described. Here we show that the ECRG4 gene is widely expressed in human tissues and report that its core promoter lies between the -780 to +420 base pairs relative to the ATG start codon of the ECRG4 open reading frame...
September 1, 2017: Gene
https://www.readbyqxmd.com/read/28870781/aberrant-g-protein-receptor-expression-is-associated-with-dna-methylation-in-aldosterone-producing-adenoma
#18
Kiyotaka Itcho, Kenji Oki, Kazuhiro Kobuke, Yoko Yoshii, Haruya Ohno, Masayasu Yoneda, Noboru Hattori
This study aimed to evaluate the methylation levels of G protein-coupled receptor (GPCR) related genes and the effects of methylation on mRNA expression levels in aldosterone-producing adenoma (APA). DNA methylation array and transcriptome analysis were applied in non-functioning adrenocortical adenoma (NFA) and APA. We investigated 192 GPCR-related genes and found hypo-methylation in the promoter region of 66 of these genes in APA. An integration study between microarray and methylation analysis revealed that HTR4, MC2R, TACR1, GRM3, and PTGER1 showed hypo-methylation and up-regulation of mRNA in APA...
September 6, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28869966/polycomb-like-proteins-link-the-prc2-complex-to-cpg-islands
#19
Haojie Li, Robert Liefke, Junyi Jiang, Jesse Vigoda Kurland, Wei Tian, Pujuan Deng, Weidi Zhang, Qian He, Dinshaw J Patel, Martha L Bulyk, Yang Shi, Zhanxin Wang
The Polycomb repressive complex 2 (PRC2) mainly mediates transcriptional repression and has essential roles in various biological processes including the maintenance of cell identity and proper differentiation. Polycomb-like (PCL) proteins, such as PHF1, MTF2 and PHF19, are PRC2-associated factors that form sub-complexes with PRC2 core components, and have been proposed to modulate the enzymatic activity of PRC2 or the recruitment of PRC2 to specific genomic loci. Mammalian PRC2-binding sites are enriched in CG content, which correlates with CpG islands that display a low level of DNA methylation...
September 14, 2017: Nature
https://www.readbyqxmd.com/read/28863210/alternatively-spliced-mefv-transcript-lacking-exon-2-and-its-protein-isoform-pyrin-2d-implies-an-epigenetic-regulation-of-the-gene-in-inflammatory-cell-culture-models
#20
Gokce Celikyapi Erdem, Sule Erdemir, Irem Abaci, Asli K Kirectepe Aydin, Elif Everest, Eda Tahir Turanli
The function of gene body DNA methylation in alternative splicing, and its relation to disease pathogenesis is not fully elucidated. The gene for familial Mediterranean fever (MEFV) encodes the pyrin protein and contains a 998 bp CpG island, covering the second exon, which is differentially methylated in FMF patients compared to healthy controls. Our further observation of increased exon 2-spliced MEFV transcript in leukocytes of FMF patients provoked us to test the role of exon methylation in alternative splicing using inflammatory cell culture models...
July 2017: Genetics and Molecular Biology
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