Dna methylation

Qiumei Feng, Li Qin, Mengying Wang, Po Wang
A promising electrochemical system was explored for DNA methylation detection according to the construction of a signal-on biosensor. Based on the ingenious design of probe DNA and auxiliary DNA, methylated target DNA triggered the exonuclease III (Exo III) digestion of auxiliary DNA from 3'-terminus, resulting in the conformational change of probe DNA with an electroactive methylene blue (MB) tag at 5'-terminus. Consequently, the MB tag in the probe DNA was close to the electrode surface for electron transfer, generating an increased current signal...
November 4, 2019: Biosensors & Bioelectronics
Yiwei Guo, Wenxiang Wang, Yiqin Chen, Yan Sun, Yuchen Li, Fangyuan Guan, Qi Shen, Yiruo Guo, Wenchang Zhang
Information on the effects of gibberellic acid (gibberellin A3, GA3) on ovarian follicle development is limited. In our present study, 21-day-old female Wistar rats were exposed to GA3 by gavage (25, 50, and 100 mg/kg body weight, once per day) for eight weeks to evaluate the influence of GA3 on ovarian follicle development. After treatment, significant (P < 0.05) increases (to 40.17% and 44.5%, respectively) in atretic follicle proportions and significant decreases (to 19.49% and 17.86%, respectively) in corpus luteum proportions were observed in the 50 and 100 mg/kg treatment groups compared to the control group...
November 13, 2019: Toxicology Letters
R Chaix, M Fagny, M Cosin-Tomás, M Alvarez-López, L Lemee, B Regnault, R J Davidson, A Lutz, P Kaliman
The human methylome is dynamically influenced by psychological stress. However, its responsiveness to stress management remains underexplored. Meditation practice has been shown to significantly reduce stress level, among other beneficial neurophysiological outcomes. Here, we evaluated the impact of a day of intensive meditation practice (t2 -t1 = 8 hours) on the methylome of peripheral blood mononuclear cells in experienced meditators (n = 17). In parallel, we assessed the influence of a day of leisure activities in the same environment on the methylome of matched control subjects with no meditation experience (n = 17)...
November 13, 2019: Brain, Behavior, and Immunity
Anna Nowicka, Barbara Tokarz, Jana Zwyrtková, Eva Dvořák Tomaštíková, Klára Procházková, Ugur Ercan, Andreas Finke, Wilfried Rozhon, Brigitte Poppenberger, Miroslav Otmar, Igor Niezgodzki, Marcela Krečmerová, Ingo Schubert, Ales Pecinka
Repetitive DNA sequences and some genes are epigenetically repressed by transcriptional gene silencing (TGS). When genetic mutants are not available or problematic to use, TGS can be suppressed by chemical inhibitors. However, informed use of epigenetic inhibitors is partially hampered by the absence of their systematic comparison. In addition, there is emerging evidence that epigenetic inhibitors cause genome instability, but the nature of this damage and its repair remain unclear. To bridge these gaps, we compared effects of 5-azacytidine (AC), 2´-deoxy-5-azacytidine (DAC), zebularine and 3-deazaneplanocin A (DZNep) on TGS and DNA damage repair...
November 16, 2019: Plant Journal
Yanyi Song, Xiang Zhou, Min Zhang, Wei Zhao, Yongmei Liu, Sharon L R Kardia, Ana V Diez Roux, Belinda L Needham, Jennifer A Smith, Bhramar Mukherjee
Causal mediation analysis aims to examine the role of a mediator or a group of mediators that lie in the pathway between an exposure and an outcome. Recent biomedical studies often involve a large number of potential mediators based on high-throughput technologies. Most of the current analytic methods focus on settings with one or a moderate number of potential mediators. With the expanding growth of -omics data, joint analysis of molecular-level genomics data with epidemiological data through mediation analysis is becoming more common...
November 16, 2019: Biometrics
Baihui Wang, Qiang Luo, Yingping Li, Liufan Yin, Nana Zhou, Xiangnan Li, Jianhua Gan, Aiwu Dong
As the largest group of MYB family transcription factors, R2R3-MYB proteins play essential roles during plant growth and development. However, the structural basis underlying how R2R3-MYBs recognize the target DNA remains elusive. Here, we report the crystal structure of Arabidopsis WEREWOLF (WER), an R2R3-MYB protein, in complex with its target DNA. Structural analysis showed that the third α-helices in both the R2 and R3 repeats of WER fit in the major groove of the DNA, specifically recognizing the DNA motif 5'-AACNGC-3'...
November 16, 2019: Nucleic Acids Research
Linlin Wang, Ju Yong Lee, Linfeng Gao, Jiekai Yin, Yaokai Duan, Luis A Jimenez, Gary Brent Adkins, Wendan Ren, Linhui Li, Jian Fang, Yinsheng Wang, Jikui Song, Wenwan Zhong
DNA methyltransferases (DNMTs) are enzymes responsible for establishing and maintaining DNA methylation in cells. DNMT inhibition is actively pursued in cancer treatment, dominantly through the formation of irreversible covalent complexes between small molecular compounds and DNMTs that suffers from low efficacy and high cytotoxicity, as well as no selectivity towards different DNMTs. Herein, we discover aptamers against the maintenance DNA methyltransferase, DNMT1, by coupling Asymmetrical Flow Field-Flow Fractionation (AF4) with Systematic Evolution of Ligands by EXponential enrichment (SELEX)...
November 16, 2019: Nucleic Acids Research
Christian Thomas, Annika Wefers, Susanne Bens, Karolina Nemes, Abbas Agaimy, Florian Oyen, Silke Vogelgesang, Fausto J Rodriguez, Francesca M Brett, Roger McLendon, Istvan Bodi, Fanny Burel-Vandenbos, Kathy Keyvani, Stefan Tippelt, Frantz R Poulsen, Eric S Lipp, Caterina Giannini, Guido Reifenberger, Klaus Kuchelmeister, Torsten Pietsch, Uwe Kordes, Reiner Siebert, Michael C Frühwald, Pascal D Johann, Martin Sill, Marcel Kool, Andreas von Deimling, Werner Paulus, Martin Hasselblatt
Atypical teratoid/rhabdoid tumor (ATRT) is a highly malignant brain tumor predominantly occurring in infants. Mutations of the SMARCB1 gene are the characteristic genetic lesion. SMARCB1-mutant tumors in adolescents and adults are rare and may show uncommon histopathological and clinical features. Here we report seven SMARCB1-deficient intracranial tumors sharing distinct clinical, histopathological and molecular features. Median age of the four females and three males was 40 years (range 15-61 years). All tumors were located in the pineal region...
November 16, 2019: Acta Neuropathologica
Sarah J Bowden, Ilkka Kalliala, Areti A Veroniki, Marc Arbyn, Anita Mitra, Kostas Lathouras, Lisa Mirabello, Marc Chadeau-Hyam, Evangelos Paraskevaidis, James M Flanagan, Maria Kyrgiou
BACKGROUND: Methylation of viral DNA has been proposed as a novel biomarker for triage of human papillomavirus (HPV) positive women at screening. This systematic review and meta-analysis aims to assess how methylation levels change with disease severity and to determine diagnostic test accuracy (DTA) in detecting high-grade cervical intra-epithelial neoplasia (CIN). METHODS: We performed searches in MEDLINE, EMBASE and CENTRAL from inception to October 2019. Studies were eligible if they explored HPV methylation levels in HPV positive women...
November 12, 2019: EBioMedicine
Jaemyung Choi, David B Lyons, M Yvonne Kim, Jonathan D Moore, Daniel Zilberman
DNA methylation and histone H1 mediate transcriptional silencing of genes and transposable elements, but how they interact is unclear. In plants and animals with mosaic genomic methylation, functionally mysterious methylation is also common within constitutively active housekeeping genes. Here, we show that H1 is enriched in methylated sequences, including genes, of Arabidopsis thaliana, yet this enrichment is independent of DNA methylation. Loss of H1 disperses heterochromatin, globally alters nucleosome organization, and activates H1-bound genes, but only weakly de-represses transposable elements...
November 4, 2019: Molecular Cell
Ahmed Abdelhameed, Xiaoping Liao, Craig A McElroy, April C Joice, Liva Rakotondraibe, Junan Li, Carla Slebodnick, Pu Guo, W David Wilson, Karl A Werbovetz
Cyanine compounds have previously shown excellent in vitro and promising in vivo antileishmanial efficacy, but the potential toxicity of these agents is a concern. A series of 22 analogs of thiazole orange ((Z)-1-methyl-4-((3-methylbenzo[d]thiazol-2(3H)-ylidene)methyl)quinolin-1-ium salt), a commercial cyanine dye with antileishmanial activity, were synthesized in an effort to increase the selectivity of such compounds while maintaining efficacy. Cyanines possessing substitutions on the quinolinium ring system displayed potency against Leishmania donovani axenic amastigotes that differed little from the parent compound (IC50 12-42 nM), while ring disjunction analogs were both less potent and less toxic...
October 4, 2019: Bioorganic & Medicinal Chemistry Letters
Shenghui Liu, Yan Zhao, Yuru Xu, Meixiang Sang, Ruili Zhao, Lina Gu, Baoen Shan
PURPOSE: Abnormal DNA methylation plays an important role in clinical diagnosis and prognosis of various tumors. DNA methylation is catalyzed by DNA methyltransferase (DNMT). However, the methylation status of MAGE-A1 and MAGE-A3 promoter regions in LSCC is unclear. To investigate the methylation levels of MAGE-A1, -A3 in LSCC and corresponding normal tissues. The expression of DNMTs (DNMT1, DNMT3a and DNMT3b) in LSCC and the relationship between the methylation status of MAGE-A1, -A3 were analyzed...
October 18, 2019: American Journal of Otolaryngology
Andrée-Anne Hudon Thibeault, Catherine Laprise
Asthma is a complex trait, often associated with atopy. The genetic contribution has been evidenced by familial occurrence. Genome-wide association studies allowed for associating numerous genes with asthma, as well as identifying new loci that have a minor contribution to its phenotype. Considering the role of environmental exposure on asthma development, an increasing amount of literature has been published on epigenetic modifications associated with this pathology and especially on DNA methylation, in an attempt to better understand its missing heritability...
November 15, 2019: Genes
Paulina Kober, Joanna Boresowicz, Natalia Rusetska, Maria Maksymowicz, Agnieszka Paziewska, Michalina Dąbrowska, Jacek Kunicki, Wiesław Bonicki, Jerzy Ostrowski, Janusz A Siedlecki, Mateusz Bujko
Gonadotroph nonfunctioning pituitary adenomas (NFPAs) are common intracranial tumors, but the role of aberrant epigenetic regulation in their development remains poorly understood. In this study, we investigated the effect of impaired CpG methylation in NFPAs. We determined DNA methylation and transcriptomic profiles in 32 NFPAs and normal pituitary sections using methylation arrays and sequencing, respectively. Ten percent of differentially methylated CpGs were correlated with gene expression, and the affected genes are involved in a variety of tumorigenesis-related pathways...
October 25, 2019: Cancers
Lars Henrik Jensen, René Olesen, Lone Noergaard Petersen, Anders Kindberg Boysen, Rikke Fredslund Andersen, Jan Lindebjerg, Lise Nottelmann, Caroline Emilie Brenner Thomsen, Birgitte Mayland Havelund, Anders Jakobsen, Torben Frøstrup Hansen
There is a need for biomarkers to improve the clinical benefit from systemic treatment of colorectal cancer. We designed a prospective, clinical study where patients receiving regorafenib as last-line treatment had sequential blood samples drawn. Effect and toxicity was monitored. The primary clinical endpoint was progression free survival (PFS). Cell-free circulating tumor (ct) DNA was measured as either the fraction with Neuropeptide Y ( NPY ) methylated DNA or KRAS/NRAS/BRAF mutated ctDNA. One hundred patients were included from three Danish centers...
October 25, 2019: Cancers
Joseph A Bellanti
The 2020 Annual Review Issue, "Preventing Disease in the 21st Century" was selected by the Editors-in-Chief of Pediatric Research to include a variety of disease entities that confront health-care practitioners entrusted to the care of infants and children. In keeping with this mandate, this article reviews the subject of epigenetics, which impacts pediatric research from bench to bedside. Epigenetic mechanisms exert their effects through the interaction of environment, various susceptibility genes, and immunologic development and include: (1) DNA methylation; (2) posttranslational modifications of histone proteins through acetylation and methylation, and (3) RNA-mediated gene silencing by microRNA (miRNA) regulation...
November 15, 2019: Pediatric Research
Bürge Ulukan, Yasemin Sila Ozkaya, Müjdat Zeybel
Fibroblasts have a central role in tissue fibrosis and fibrotic diseases. Fibroblast activation is regulated by several mechanisms including epigenetic modifications; histone modifications, DNA methylation and non-coding RNAs. Although research has significantly contributed to our basic understanding of fibrotic diseases over the last decade, cooperative activity of epigenetic mechanisms demonstrates the complexity of fibrogenesis. This review will summarise the latest epigenetic advances in fibroproliferative diseases...
November 12, 2019: Current Opinion in Pharmacology
Aline Ribeiro Borçoi, Suzanny Oliveira Mendes, Joaquim Gasparini Dos Santos, Mayara Mota de Oliveira, Ivana Alece Arantes Moreno, Flávia Vitorino Freitas, Júlia Assis Pinheiro, Juliana Krüger Arpini, Ester Ribeiro Cunha, Anderson Barros Archanjo, Aricia Leone Evangelista Monteiro de Assis, Bruna Pereira Sorroche, Lídia Maria Rebolho Batista Arantes, Elizeu Borloti, Adriana Madeira Álvares-da-Silva
OBJECTIVE: The aim of this study was to verify determinant factors for depression and analyze the relationship between possible changes in HPA axis and depression, in this case NR3C1 DNA methylation and serum cortisol levels. METHODS: 349 adult volunteers were recruited to evaluate depression, socio-demographic, economic and lifestyle factors, serum cortisol levels and NR3C1 DNA methylation by pyrosequencing. Depression determinant factors were investigated using a Poisson regression model with robust variance (p < 0...
October 16, 2019: Journal of Psychiatric Research
Ruiwen Li, Wei Guo, Lei Lei, Ling Zhang, Yunhao Liu, Jian Han, Lianguo Chen, Bingsheng Zhou
Early-life exposure to toxicants could affect health outcomes in adulthood. We determined the effects of early-life exposure to the organophosphorus flame-retardant tris (1,3-dichloro-2-propyl) phosphate (TDCIPP) in adult zebrafish. Embryos were exposed to TDCIPP from early embryogenesis (2 h post-fertilization) to 10 days post-fertilization (dpf), and larvae were transferred to clean water until adulthood (150 dpf). TDCIPP showed accumulation in larvae, but returned to control levels after 7 days of depuration...
November 12, 2019: Environment International
Meiping Tian, Benhua Zhao, Francis L Martin, Camilo L M Morais, Liangpo Liu, Qingyu Huang, Jie Zhang, Heqing Shen
Exposure to environmental pollutant organochlorine pesticides (OCPs) and the role of tumour suppressor GSTs gene polymorphisms as well as epigenetic alterations have all been well reported in hepatocarcinogenesis. However, the interplay between environmental risk factors and polymorphic tumour suppressor genes or epigenetic factors in hepatocellular carcinoma (HCC) development remains ambiguous. Herein, we investigated the relationship of three GSTs polymorphisms (GSTT1 deletion, GSTM1 deletion, GSTP1 rs1695) as well as GSTP1 promoter region DNA methylation and HCC risk with a particular focus on the interaction with OCPs exposure among 90 HCC cases and 99 controls in a Chinese population...
November 12, 2019: Environment International
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