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Methylation of sites CpG in promoter

Zhen Yang, Andrew Wong, Diana Kuh, Dirk S Paul, Vardhman K Rakyan, R David Leslie, Shijie C Zheng, Martin Widschwendter, Stephan Beck, Andrew E Teschendorff
BACKGROUND: Variation in cancer risk among somatic tissues has been attributed to variations in the underlying rate of stem cell division. For a given tissue type, variable cancer risk between individuals is thought to be influenced by extrinsic factors which modulate this rate of stem cell division. To date, no molecular mitotic clock has been developed to approximate the number of stem cell divisions in a tissue of an individual and which is correlated with cancer risk. RESULTS: Here, we integrate mathematical modeling with prior biological knowledge to construct a DNA methylation-based age-correlative model which approximates a mitotic clock in both normal and cancer tissue...
October 3, 2016: Genome Biology
Sern-Yih Cheah, Robert McLeay, Leesa F Wockner, Bruce R Lawford, Ross McD Young, Charles P Morris, Joanne Voisey
OBJECTIVE: To examine the combined effect of the BDNF Val66Met (rs6265) polymorphism and BDNF DNA methylation on transcriptional regulation of the BDNF gene. METHODS: DNA methylation profiles were generated for CpG sites proximal to Val66Met, within BDNF promoter I and exon V for prefrontal cortex samples from 25 schizophrenia and 25 control subjects. Val66Met genotypes and BDNF mRNA expression data were generated by transcriptome sequencing. Expression, methylation and genotype data were correlated and examined for association with schizophrenia...
October 7, 2016: World Journal of Biological Psychiatry
Vincent Huin, Vincent Deramecourt, Dominique Caparros-Lefebvre, Claude-Alain Maurage, Charles Duyckaerts, Eniko Kovari, Florence Pasquier, Valérie Buée-Scherrer, Julien Labreuche, Hélène Behal, Luc Buée, Claire-Marie Dhaenens, Bernard Sablonnière
BACKGROUND: Progressive supranuclear palsy (PSP) is a rare neurodegenerative disease causing parkinsonian symptoms. Altered DNA methylation of the microtubule-associated protein tau gene correlates with the expression changes in Alzheimer's disease and Parkinson's disease brains. However, few studies examine the sequences beyond the constitutive promoter. OBJECTIVES: Because activating different microtubule-associated protein tau gene control regions via methylation might regulate the differential tau expression constituting the specific signatures of individual tauopathies, we compared methylation of a candidate promoter, intron 0...
October 6, 2016: Movement Disorders: Official Journal of the Movement Disorder Society
Yasser Vega, Sergio Arias, Irene Paradisi
Martin-Bell syndrome is mainly caused by the expansion of CGG trinucleotide repeats (>200 CGG) in the first exon of the FMR1 gene, leading to hypermethylation of the promoter region and silencing of the FMR1 protein expression. These changes are responsible for a phenotype with varying degrees of mental retardation, a long face with large and protruding ears, macroorchidism and autistic behavior. There may also be, however, patients who exhibit typical features of the syndrome without any expansion in the FMR1 gene; thus, other mechanisms affecting the expression of the FMR1 gene were assessed in 25 out of 29 ascertained patients with the typical phenotype without full mutation...
October 6, 2016: Journal of Human Genetics
Ryo Shimizu, Tomoya Muto, Kazumasa Aoyama, Kwangmin Choi, Masahiro Takeuchi, Shuhei Koide, Nagisa Hasegawa, Yusuke Isshiki, Emi Togasaki, Chika Kawajiri-Manako, Yuhei Nagao, Shokichi Tsukamoto, Shio Sakai, Yusuke Takeda, Naoya Mimura, Chikako Ohwada, Emiko Sakaida, Tohru Iseki, Daniel T Starczynowski, Atsushi Iwama, Koutaro Yokote, Chiaki Nakaseko
Expression of the tumor suppressor gene NR4A3 is silenced in the blasts of acute myeloid leukemia (AML), irrespective of the karyotype. Although the transcriptional reactivation of NR4A3 is considered to have a broad-spectrum anti-leukemic effect, the therapeutic modalities targeting this gene have been hindered by our minimal understanding of the transcriptional mechanisms regulating its expression, particularly in human AML. Here we show the role of intragenic DNA hypermethylation in reducing the expression of NR4A3 in AML...
September 26, 2016: Leukemia Research
Amir Pozner, Tommy W Terooatea, Bethany A Buck-Koehntop
The correlation between aberrant DNA methylation with cancer promotion and progression has prompted an interest in discerning the associated regulatory mechanisms. Kaiso (ZBTB33) is a specialized transcription factor that selectively recognizes methylated CpG-containing sites as well as a sequence-specific DNA target. Increasing reports link ZBTB33 overexpression and transcriptional activities with metastatic potential and poor prognosis in cancer, though there is little mechanistic insight into how cells harness ZBTB33 transcriptional capabilities to promote and progress disease...
September 30, 2016: Journal of Biological Chemistry
Xin-Gang Li, Ning Ma, Bo Wang, Xiao-Qing Li, Sheng-Hui Mei, Kun Zhao, Yong-Jun Wang, Wei Li, Zhi-Gang Zhao, Shu-Sen Sun, Zhong-Rong Miao
The primary mechanism of clopidogrel resistance is still unclear. We aimed to investigate whether the methylation status of the P2Y12 promoter has effects on platelet function and clinical ischemic events. Patients with ischemic cerebrovascular disease were enrolled into our study. Venous blood samples were drawn for thrombelastograpy (TEG) and active metabolite assay. Patients were divided into a case- or control-group based on the occurrence of ischemic events during a one year follow-up. Two TEG parameters between the case and control groups were statistically significant [ADP inhibition rate (ADP%): P = 0...
September 30, 2016: Scientific Reports
Kiyoshi Misawa, Daiki Mochizuki, Shiori Endo, Masato Mima, Yuki Misawa, Atsushi Imai, Kazuya Shinmura, Takeharu Kanazawa, Thomas E Carey, Hiroyuki Mineta
BACKGROUND: The aim of this study was to evaluate the prognostic value of the promoter methylation status of galanin (GAL) and galanin receptor 1/2 (GALR1/2) by assessing their association with disease-free survival and known prognostic factors in head and neck cancer. METHODS: We generated methylation profiles of GAL and GALR1/2 in tumor samples obtained from 202 patients with head and neck squamous cell carcinoma (HNSCC); these included 43 hypopharynx, 42 larynx, 59 oral cavity, and 58 oropharynx tumor samples...
September 29, 2016: Molecular Carcinogenesis
Kristina Schwender, Hannah Holtkötter, Kristina Schulze Johann, Alina Glaub, Marianne Schürenkamp, Ulla Sibbing, Sabrina Banken, Mechtild Vennemann, Heidi Pfeiffer, Marielle Vennemann
PURPOSE: Smoking during pregnancy has long been known as an important risk factor for sudden infant death syndrome (SIDS). However, the precise relationship between the smoking behavior of the mother and SIDS still remains unclear. In this study, the influence of prenatal smoking exposure on the childrens' DNA methylation state of a CpG island located upstream of the promoter of the growth factor independent 1 (GFI1) gene was analyzed. METHODS: Blood samples of well-defined SIDS cases with non-smoking mothers (n = 11), SIDS cases with smoking mothers during pregnancy (n = 11), and non-SIDS cases (n = 6) were obtained from a previous study and methylation states were determined by bisulfite sequencing...
September 27, 2016: Forensic Science, Medicine, and Pathology
Kaijing Ding, Jianzhong Yang, Gavin P Reynolds, Bing Chen, Jingru Shao, Ruixiang Liu, Qiujin Qian, Hua Liu, Runxu Yang, Jianfan Wen, Chuanyuan Kang
OBJECTIVES: To examine the association of the DNA methylation of DAT1 and DRD4 gene with methylphenidate (MPH) response in attention deficit hyperactivity disorder (ADHD). METHODS: One hundred and eleven DSM-IV defined ADHD Chinese Han children were recruited. Inattention, hyperactivity-impulsivity and oppositional symptoms were evaluated by the Swanson, Nolan and Pelham-IV-parent rating scale (SNAP-IV-P) at baseline and 6 weeks after MPH treatment. DNA methylation of CpG sites in the promoter sequences of DAT1 and DRD4 was examined for association with treatment response...
September 27, 2016: World Journal of Biological Psychiatry
Xinyu Zhang, Amy C Justice, Ying Hu, Zuoheng Wang, Hongyu Zhao, Guilin Wang, Eric O Johnson, Brinda Emu, Richard E Sutton, John H Krystal, Ke Xu
Epigenetic control of human immunodeficiency virus-1 (HIV-1) genes is critical for viral integration and latency. However, epigenetic changes in the HIV-1-infected host genome have not been well characterized. Here, we report the first large-scale epigenome-wide association study of DNA methylation for HIV-1 infection. We recruited HIV-infected (n = 261) and uninfected (n = 117) patients from the Veteran Aging Cohort Study (VACS) and all samples were profiled for 485,521 CpG sites in DNA extracted from the blood...
August 12, 2016: Epigenetics: Official Journal of the DNA Methylation Society
Jiantao Zhang, Wenli Zhou, Ying Liu, Nan Li
Down syndrome (DS) is the most common birth defect in children. To investigate the mechanisms of DS, the present study analyzed the bisulfite‑sequencing (seq) data GSE42144, which was downloaded from the Gene Expression Omnibus. GSE42144 included DNA methylation data of three DS samples and three control samples, and RNA‑seq data of two DS samples and five control samples. The methylated sites in the bisulfite‑seq data were detected using Bismark and Bowtie2. The BiSeq tool was applied to determine differentially methylated regions and to identify adjacent genes...
September 26, 2016: Molecular Medicine Reports
Wuyun Dalai, Eiko Matsuo, Natsumi Takeyama, Junichi Kawano, Keiichi Saeki
The cellular isoform of the prion protein (PrP(C)) plays critical roles in the development of prion disorders. Although PrP mRNA is ubiquitously present in a tissue-specific manner, the DNA methylation of PrP gene (Prnp) is still unknown. In this study, we demonstrated that the CpG island (CGI, positioned at -218 to +152 bp from the transcriptional start site) including the Prnp core promoter region was completely unmethylated in all tested tissues. On the other hand, CpG methylation in the CGI shore region (positioned at -599 to -238 bp) occurred in various tissue- and site-specific proportions...
September 26, 2016: Journal of Veterinary Medical Science
Jing Shen, Shengru Wu, Wei Guo, Saisai Liang, Xueyuan Li, Xiaojun Yang
Inflammatory response which can be mediated by inflammatory genes, can be induced by pathogenic microorganisms, be associated with enteric diseases and the loss of growth performance in broilers. The understanding of epigenetic regulation of inflammatory genes could help explain the response to infection of microorganisms and inhibit the reaction of inflammation in broilers. This study investigated the effect of histone acetylation by histone deacetylases (HDAC) inhibitors trichostain A (TSA) and DNA methylation by demethylation agent 5-Aza-2'-deoxycytidine (AZA) and methyl donor methionine (Met) and folic acid (FA) on the expression of pro-inflammatory cytokines in lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMC) from healthy broilers...
September 18, 2016: Immunobiology
Na Wang, Fang Sui, Jingjing Ma, Xi Su, Jiazhe Liu, Demao Yao, Bingyin Shi, Peng Hou, Qi Yang
BACKGROUND AND AIMS: Methylation status of RUNX3 remains largely unknown in gastric cancer (GC). The aim of this study was to prognostically evaluate the methylation level of CpG sites within RUNX3 promoter region in GC. METHODS: Using pyrosequencing, we quantitatively explored the methylation status of 8 CpG sites within RUNX3 promoter region for 76 gastric cancer and 24 normal gastric tissues. We then analyzed the association between methylation level of each CpG site and clinicopathological characteristics and outcomes in the cohort...
May 2016: Archives of Medical Research
Qiaomu Hu, Haifeng Tian, Yan Meng, Hanbing Xiao
Lhx9 is an LIM (named for the first three proteins in which the domain was found, Lin-11, Isl1 and Mec-3) homeodomain protein involved in development and differentiation of the gonad. In this study, we isolated the full-length Lhx9 and Lhx9α from Andrias davidianus, detected the tissue distribution and analysed the methylation of the promoters. We identified Lhx9 of 1411 bp and Lhx9α of 1153-bp length, differing in the 3'-flanking region, encoding 399 and 330 amino acids, respectively. The Lhx9 gene was detected primarily in liver, ovary and heart with moderate expression in brain, pituitary, intestine and spleen, and low expression in the remaining examined tissues, while Lhx9α expression was high in heart, pituitary and liver, and low in spleen and stomach...
September 2016: Journal of Genetics
Hirokazu Muraoka, Kazuhiro Hasegawa, Shu Wakino
OBJECTIVE: Nicotinamide phosphoribosyltransferase (Nampt) cooperates with a longevity gene, Sirt1, to exert the potentiation of stress resistance. We have reported that the high expression level of Nampt in PTs contributes to the sufficient supply of NMN to glomeruli. We also showed that downregulation of Nampt and NMN in PT in DN leads to glomerular damages (Nature Medicine 2013). However, the regulation mechanisms of Nampt expression remain unknown. DESIGN AND METHOD: We investigated how Nampt expression is consistently retained at high levels in PTs under normal conditions and how Nampt levels are decreased in DN...
September 2016: Journal of Hypertension
Saeed Aslani, Mahdi Mahmoudi, Masoud Garshasbi, Ahmad Reza Jamshidi, Jafar Karami, Mohammad Hossein Nicknam
Ankylosing spondylitis (AS) is an autoimmune disease with a chronic inflammatory arthritis. The critical role of methylation in the biology of immunocytes has increasingly been surveyed to discover disease etiology. DNA methyltransferase 1 (DNMT1) is an enzyme, which establishes and regulates patterns of methylated cytosine residues. The aim of the current investigation was to unveil if methylation circumstances of CpG sites in DNMT1 promoter could affect the mRNA expression level of this gene in peripheral blood mononuclear cells (PBMCs) from AS patients...
November 2016: Clinical Rheumatology
Subhojit Sen, Kirsten F Block, Alice Pasini, Stephen B Baylin, Hariharan Easwaran
BACKGROUND: Bivalent chromatin refers to overlapping regions containing activating histone H3 Lys4 trimethylation (H3K4me3) and inactivating H3K27me3 marks. Existence of such bivalent marks on the same nucleosome has only recently been suggested. Previous genome-wide efforts to characterize bivalent chromatin have focused primarily on individual marks to define overlapping zones of bivalency rather than mapping positions of truly bivalent mononucleosomes. RESULTS: Here, we developed an efficacious sequential ChIP technique for examining global positioning of individual bivalent nucleosomes...
2016: BMC Medical Genomics
Hong-Peng Zuo, Ying-Yu Guo, Lin Che, Xian-Zheng Wu
BACKGROUND: Interleukin-6 (IL-6) is implicated in the pathogenesis of coronary heart disease (CHD), and IL-6 expression has associated with reduced DNA methylation of its gene promoter. However, there are no data on IL-6 promoter methylation and the risk of CHD. OBJECTIVE: To examine whether IL-6 promoter methylation measured in blood leukocyte DNA is associated with CHD risk. METHODS: A total of 212 cases with CHD and 218 controls were enrolled...
August 2016: Arquivos Brasileiros de Cardiologia
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