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CpG methylation

Zhijun Zeng, Xia Huo, Yu Zhang, Machteld N Hylkema, Yousheng Wu, Xijin Xu
This study explored the effects of maternal exposure to e-waste environmental heavy metals on neonatal DNA methylation patterns. Neonatal umbilical cord blood (UCB) samples were collected from participants that resided in an e-waste recycling area, Guiyu and a nearby non-e-waste area, Haojiang in China. The concentrations of UCB lead (Pb), cadmium (Cd), manganese (Mn) and chromium (Cr) were measured by graphite furnace atomic absorption spectrometry. Epigenome-wide DNA methylation at 473, 844 CpG sites (CpGs) were assessed by Illumina 450 K BeadChip...
January 6, 2019: Environmental Research
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
Yuko Kurushima, Pei-Chien Tsai, Juan Castillo-Fernandez, Alexessander Couto Alves, Julia Sarah El-Sayed Moustafa, Caroline Le Roy, Tim D Spector, Mark Ide, Francis J Hughes, Kerrin S Small, Claire J Steves, Jordana T Bell
BACKGROUND: Genetic and environmental risk factors contribute to periodontal disease, but the underlying susceptibility pathways are not fully understood. Epigenetic mechanisms are malleable regulators of gene function that can change in response to genetic and environmental stimuli, thereby providing a potential mechanism for mediating risk effects in periodontitis. The aim of this study is to identify epigenetic changes across tissues that are associated with periodontal disease. METHODS: Self-reported gingival bleeding and history of gum disease, or tooth mobility, were used as indicators of periodontal disease...
February 13, 2019: Clinical Epigenetics
Shenglin Liu, Anne Aageaard, Jesper Bechsgaard, Trine Bilde
Variation in DNA methylation patterns among genes, individuals, and populations appears to be highly variable among taxa, but our understanding of the functional significance of this variation is still incomplete. We here present the first whole genome bisulfite sequencing of a chelicerate species, the social spider Stegodyphus dumicola . We show that DNA methylation occurs mainly in CpG context and is concentrated in genes. This is a pattern also documented in other invertebrates. We present RNA sequence data to investigate the role of DNA methylation in gene regulation and show that, within individuals, methylated genes are more expressed than genes that are not methylated and that methylated genes are more stably expressed across individuals than unmethylated genes...
February 12, 2019: Genes
Suman Lee
Low-density lipoprotein Receptor Related Protein 1B (LRP1B) is homologous to the gigantic lipoprotein receptor-related protein 1 that belongs to the family of Low-density lipoprotein receptors. Previous genetic association studies of the LRP1B gene have shown its genetic association with obesity. Through exome sequencing of the LRP1B gene from a childhood severe obesity cohort (n = 692), we found novel single nucleotide polymorphism (rs431809) in intron 4, which has been significantly correlated with both body mass index (BMI) and waist-hip-ratio (WHR)...
February 12, 2019: Scientific Reports
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
Toshikazu Ushijima, Hiromu Suzuki
In this issue of Cancer Cell, Tao et al. provide compelling evidence that aging-like DNA methylation of multiple CpG islands, the CpG island methylator phenotype (CIMP), produces a cellular context that can tolerate BRAF activation avoiding senescence by dedicating 5-month culture of colon-derived organoids to epigenomic and stemness analysis.
February 11, 2019: Cancer Cell
Jennifer Pasquier, Mark Spurgeon, Martina Bradic, Binitha Thomas, Amal Robay, Omar Chidiac, Marie-Joe Dib, Rebal Turjoman, Alexandra Liberska, Michelle Staudt, Khalid A Fakhro, Robert Menzies, Amin Jayyousi, Mahmoud Zirie, Jassim Al Suwaidi, Rayaz A Malik, Talal Talal, Arash Rafii, Jason Mezey, Juan Rodriguez-Flores, Ronald G Crystal, Charbel Abi Khalil
AIM: To assess whether DNA methylation of monocytes play a role in the development of acute diabetic Charcot foot (CF). PATIENTS & METHODS: We studied the whole methylome (WM) of circulating monocytes in 18 patients with Type 2 diabetes (T2D) and acute CF, 18 T2D patients with equivalent neuropathy and 18 T2D patients without neuropathy, using the enhanced reduced representation bisulfite sequencing technique. RESULTS & CONCLUSION: WM analysis demonstrated that CF monocytes are differentially methylated compared with non-CF monocytes, in both CpG-site and gene-mapped analysis approaches...
February 2019: Epigenomics
Cassandra J Meakin, Elizabeth M Martin, John T Szilagyi, Leena A Nylander-French, Rebecca C Fry
Prenatal exposure to inorganic arsenic (iAs) has been associated with adverse developmental and reproductive outcomes. These outcomes may be tied to altered functionality of nuclear transcription factors such as the glucocorticoid receptor (GR) in the placenta and associated gene expression. The GR pathway is integral for proper fetal and placental development, and perturbations in this pathway may underlie observed associations between prenatal iAs exposure and adverse birth outcomes. We therefore set out to investigate whether iAs modulates the GR signaling pathway in placental cells...
February 12, 2019: Chemical Research in Toxicology
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
Yinghong Zhang, Yangyang Chen, Hongmei Qu, Yuanli Wang
BACKGROUND: Gestational diabetes mellitus (GDM) is defined as any degree of glucose intolerance during pregnancy, and will lead to high risk of diabetes even after pregnancy. Hypoxia-inducible factor (HIF) family proteins are transcriptional factors that are highly correlated with methylation, which might be involved in the regulation of GDM. METHODS: Baseline clinical characteristics of the GDM patients and healthy women were analyzed. Omental tissue from GDM patients and control groups were collected and detected for the expression levels of HIF1A, HIF2A, and HIF3A...
February 11, 2019: Molecular Genetics & Genomic Medicine
Tomer Cramer, Tali Rosenberg, Tatiana Kisliouk, Noam Meiri
Stressful events in early life might lead to stress resilience or vulnerability, depending on an adjustable stress-response set-point, which can be altered during postnatal sensory development and involves epigenetic regulation of corticotropin-releasing hormone (CRH). During the critical developmental period of thermal-control establishment in 3-day-old chicks, heat stress was found to affect both body temperature and expression of CRH in the hypothalamic paraventricular nucleus. Both increased during heat challenge in vulnerable chicks, whereas they decreased in resilient chicks...
October 19, 2018: Molecular Psychiatry
Lixian Wang, Jian Zhao, Yan Li, Zihe Wang, Shan Kang
Endometriosis is a common chronic gynecologic disorder characterized by the presence and growth of endometrial-like tissue outside of the uterine cavity. Although the exact etiology remains unclear, epigenetic modifications, such as DNA methylation, are thought to contribute to the pathogenesis of endometriosis. Here, we used the Illumina Human Methylation 450 K BeadChip Array to analyze the genome-wide DNA methylation profiles of six endometriotic lesions and six eutopic endometria from patients with ovarian endometriosis and six endometria of women without endometriosis...
February 11, 2019: Molecular Reproduction and Development
Sirisha Marreddy Cheedipudi, Scot J Matkovich, Cristian Coarfa, Xin Hu, Matthew J Robertson, Mary E Sweet, Matthew Taylor, Luisa Mestroni, Joseph C Cleveland, James T Willerson, Priyatansh Gurha, Ali J Marian
RATIONALE: Lamin A/C (LMNA), a nuclear membrane protein, interacts with genome through lamin-associated domains (LADs) and regulates gene expression. Mutations in the LMNA gene cause a diverse array of diseases, including dilated cardiomyopathy (DCM). DCM is the leading cause of death in laminopathies. OBJECTIVE: To identify LADs and characterize their associations with CpG methylation and gene expression in human cardiac myocytes in DCM. METHODS AND RESULTS: LMNA chromatin immunoprecipitation-sequencing, reduced representative bisulfite sequencing, and RNA-sequencing were performed in 5 control and 5 LMNA-associated DCM hearts...
February 11, 2019: Circulation Research
Rocco Cappellesso, Marcello Lo Mele, Giada Munari, Erik Rosa-Rizzotto, Ennio Guido, Franca De Lazzari, Pierluigi Pilati, Marco Tonello, Fabio Farinati, Stefano Realdon, Matteo Fassan, Massimo Rugge
Colorectal cancer (CRC) is a heterogeneous group of diseases both from the morphological and molecular point of view. The sessile serrated adenoma/polyp (SSA/P) has been proposed as the precursor lesion of CRCs characterized by CpG island methylator phenotype (CIMP), DNA mismatch repair (MMR) system deficiency, and BRAF gene mutations. However, no study so far investigated the molecular landscape of "sessile serrated" adenoma to carcinoma transition in early CRCs. Six formalin-fixed paraffin-embedded CRCs developed within SSA/P were profiled for the immunohistochemical expression of MMR proteins (MLH1, MSH2, MSH6, PMS2, and Ep-CAM), p16, and β-catenin...
February 3, 2019: Pathology, Research and Practice
Huichuan Yu, Liangliang Bai, Guannan Tang, Xiaolin Wang, Meijin Huang, Guangwen Cao, Jianping Wang, Yanxin Luo
BACKGROUND: The DNA methylation profile provides valuable biological information with potential clinical utility. Several methods, such as quantitative methylation-specific PCR (qMSP), have been developed to examine methylation of specific CpG sites. Existing qMSP-based techniques fail to examine the genomic methylation at a single-base resolution, particularly for loci in gene bodies or extensive CpG open seas lacking flanking CpGs. Therefore, we established a novel assay for quantitative analysis of single-base methylation...
February 8, 2019: Clinical Chemistry
Jesper Beltoft Lund, Shuxia Li, Jan Baumbach, Anne Marie Svane, Jacob Hjelmborg, Lene Christiansen, Kaare Christensen, Paul Redmond, Riccardo E Marioni, Ian J Deary, Qihua Tan
BACKGROUND: Multiple epigenome-wide association studies have been performed to identify DNA methylation patterns regulated by aging or correlated with risk of death. However, the inter-relatedness of the epigenetic basis of aging and mortality has not been well investigated. METHODS: Using genome-wide DNA methylation data from the Lothian Birth Cohorts, we conducted a genome-wide association analysis of all-cause mortality and compared this with age-associated methylation patterns reported on the same samples...
February 8, 2019: Clinical Epigenetics
Seçkin Akgül, Ann-Marie Patch, Rochelle C J D'Souza, Pamela Mukhopadhyay, Katia Nones, Sarah Kempe, Stephen H Kazakoff, Rosalind L Jeffree, Brett W Stringer, John V Pearson, Nicola Waddell, Bryan W Day
Glioblastomas are the most common and lethal neoplasms of the central nervous system. Neighbouring glioma cells maintain extreme degrees of genetic and phenotypic variation that form intratumoural heterogeneity. This genetic diversity allows the most adaptive tumour clones to develop treatment resistance, ultimately leading to disease recurrence. We aimed to model this phenomenon and test the effectiveness of several targeted therapeutic interventions to overcome therapy resistance. Heterogeneous tumour masses were first deconstructed into single tumour cells, which were expanded independently as single-cell clones...
February 6, 2019: Cancers
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