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CpG methylation

Rui-Chao Chai, Ke-Nan Zhang, Yu-Qing Liu, Fan Wu, Zheng Zhao, Kuan-Yu Wang, Tao Jiang, Yong-Zhi Wang
AIMS: The pyrosequencing (PSQ) has been regarded as the gold standard for MGMT promoter methylation testing in gliomas. However, various CpG combinations are currently used in clinical practice. We aimed to clarify how and how many CpGs combined is robust enough to predict MGMT mRNA expression and therapeutic prognosis of patients. METHODS: Total 223 patients with WHO III/IV gliomas were enrolled from Chinese Glioma Genome Atlas, including two independent cohorts, the eight-site cohort (with CpGs 75-82 tested) and the seven-site cohort (with CpGs 72-78 tested)...
August 16, 2018: CNS Neuroscience & Therapeutics
Buch Lipi, Langhnoja Jaldeep, Pillai Prakash
Astrocytes perform several critical functions such as promoting neuronal maturation, neuronal survival, maintaining and supporting neurons and oligodendrocytes. Astrocytes participate in the formation of nodes of Ranvier. Recently, studies emphasizing on the role of astrocytes in regulating myelination by secreting pro-myelinating factors like growth factors, neurotrophins and ECM proteins, have been investigated by many researchers. Methyl-CpG-Binding Protein 2 (MeCP2), an epigenetic protein, binds to CpG islands in the genome and induces multiple gene regulatory functions by conforming changes in the chromatin structure and resulting in cell-specific gene expression...
August 16, 2018: Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale
Minoru Koi, Yoshiki Okita, John M Carethers
It has been recently reported that the population of Fusobacterium , particularly Fusobacterium nucleatum ( Fn ), is overrepresented in colorectal cancers and adenomas. The promoting effects of Fn infection on adenoma and/or carcinoma formation have been shown in ApcMin/+ mice. Characteristics of Fn -associated CRC were identified through studies using human CRC cohorts, and include right-sided colon location, CpG island methylation phenotype-high (CIMP-H), high level of microsatellite instability (MSI-H), and poor patient prognosis...
2018: J Anus Rectum Colon
Yong Li, Yi Jin Liew, Guoxin Cui, Maha J Cziesielski, Noura Zahran, Craig T Michell, Christian R Voolstra, Manuel Aranda
The symbiotic relationship between cnidarians and dinoflagellates is the cornerstone of coral reef ecosystems. Although research has focused on the molecular mechanisms underlying this symbiosis, the role of epigenetic mechanisms, that is, the study of heritable changes that do not involve changes in the DNA sequence, is unknown. To assess the role of DNA methylation in the cnidarian-dinoflagellate symbiosis, we analyzed genome-wide CpG methylation, histone associations, and transcriptomic states of symbiotic and aposymbiotic anemones in the model system Aiptasia...
August 2018: Science Advances
Ruchi Shah, Karina Reyes-Gordillo, Ying Cheng, Ravi Varatharajalu, Joseph Ibrahim, M Raj Lakshman
Thymosin beta 4 (T β 4), an actin-sequestering protein, is involved in tissue development and regeneration. It prevents inflammation and fibrosis in several tissues. We investigated the role of T β 4 in chronic ethanol- and acute lipopolysaccharide- (LPS-) induced mouse liver injury. C57BL/6 mice were fed 5% ethanol in liquid diet for 4 weeks plus binge ethanol (5 g/kg, gavage) with or without LPS (2 mg/kg, intraperitoneal) for 6 hours. T β 4 (1 mg/kg, intraperitoneal) was administered for 1 week. We demonstrated that T β 4 prevented ethanol- and LPS-mediated increase in liver injury markers as well as changes in liver pathology...
2018: Oxidative Medicine and Cellular Longevity
Emma Nilsson, Anna Benrick, Milana Kokosar, Anna Krook, Eva Lindgren, Thomas Källman, Mihaela M Martis, Kurt Højlund, Charlotte Ling, Elisabet Stener-Victorin
Context: Insulin resistance in skeletal muscle is a major risk factor for the development of type 2 diabetes in women with polycystic ovary syndrome (PCOS). Despite this, the mechanisms underlying insulin resistance in PCOS are largely unknown. Objective: To investigate the genome-wide DNA methylation and gene expression patterns in skeletal muscle from women with PCOS and controls and relate to phenotypic variation. Design/Participants: In a case-control study, skeletal muscle biopsies from women with PCOS (n=17) and age, weight and BMI matched controls (n=14) were analyzed by array-based DNA methylation and mRNA expression profiling...
August 2, 2018: Journal of Clinical Endocrinology and Metabolism
Rodolfo Martín-Del-Campo, Annelisse Bárcenas-Ibarra, Itzel Sifuentes-Romero, Raúl Llera-Herrera, Alejandra García-Gasca
Normal development involves the interplay of genetic and epigenetic regulatory mechanisms. Pax6 is an eye-selector factor responsible for initiating the regulatory cascade for the development of the eyes. For the olive ridley sea turtle (Lepidochelys olivacea), a threatened species, eye malformations have been reported. In order to study the DNA methylation status of the putative promoter of the Pax6 gene in embryos with ocular malformations, an exploratory study was carried out in which DNA was isolated from embryos with anophthalmia, microphthalmia, and cyclopia, as well as from their normal counterparts...
August 12, 2018: Mechanisms of Development
Congru Li, Yong Fan, Guoqiang Li, Xiaocui Xu, Jialei Duan, Rong Li, Xiangjin Kang, Xin Ma, Xuepeng Chen, Yuwen Ke, Jie Yan, Ying Lian, Ping Liu, Yue Zhao, Hongcui Zhao, Yaoyong Chen, Yang Yu, Jiang Liu
DNA methylation plays important roles during development. However, the DNA methylation reprogramming of functional elements has not been fully investigated during mammalian embryonic development. Herein, using our modified MethylC-Seq library generation method and published post-bisulphite adapter-tagging (PBAT) method, we generated genome-wide DNA methylomes of human gametes and early embryos at single-base resolution and compared them with mouse methylomes. We showed that the dynamics of DNA methylation in functional elements are conserved between humans and mice during early embryogenesis, except for satellite repeats...
2018: Cell Discovery
Can Jiang, Jun Guo, Huaiyan Cheng, Ying-Hong Feng
Poor homing of cells after transplantation is an unresolved common issue in cardiac cell therapies. To enhance stem cell homing, the ligand CXC motif chemokine 12 (CXCL12) and its specific receptor CXC receptor type 4 (CXCR4) have been employed as a system in this study to show that induced expression of the endogenous CXCR4 gene in mouse-induced pluripotent stem cells (iPSCs) improved the cell migration. Loci-specific epigenome editing in the form of CpG demethylation at CXCR4 promoter region of the mouse iPSCs was accomplished with CXCR4b-TAL-Tet1c, chimeric fusion proteins of the catalytic domain of ten-eleven translocation 1 (TET1) to the C-terminal end of the DNA binding domains of predesigned synthetic transcription activator-like effectors (TALEs) that recognize specific DNA sequences within the mouse CXCR4 promoter region...
August 13, 2018: Inflammation
Ryan T Ash, Paul G Fahey, Jiyoung Park, Huda Y Zoghbi, Stelios M Smirnakis
MECP2 duplication syndrome is an X-linked form of syndromic autism caused by genomic duplication of the region encoding methyl-CpG-binding protein 2 (MECP2). Mice overexpressing MECP2 demonstrate social impairment, behavioral inflexibility, and altered patterns of learning and memory. Previous work showed abnormally increased stability of dendritic spines formed during motor training in the apical tuft of primary motor cortex (area M1) corticospinal neurons in the MECP2 duplication mouse model. In the current study, we measure the structural plasticity of axonal boutons in layer 5 pyramidal neuron projections to layer 1 of area M1 during motor training...
May 2018: ENeuro
Chiung-Yu Hung, Hao Zhang, Natalia Castro-Lopez, Gary R Ostroff, Payam Khoshlenar, Ambily Abraham, Garry T Cole, Austin Negron, Thomas Forsthuber, Tao Peng, John N Galgiani, Neil M Ampel, Jieh-Juen Yu
Developing an effective and safe recombinant vaccine requires microbe-specific antigens combined with an adjuvant/delivery system to strengthen protective immunity. In this study, we designed and expressed a multivalent, recombinant Coccidioides polypeptide antigen (rCpa1) that consists of three previously identified antigens (i.e., Ag2/Pra, Cs-Ag and Pmp1) and 5 pathogen-derived peptides with high affinity for human MHC II molecules. The purified rCpa1 was encapsulated into four types of yeast cell-wall particles containing various compositions of β-glucan, mannan and chitin or mixed with an oligonucleotide (ODN) containing 2 methylated dinucleotide CpG motifs...
August 13, 2018: Infection and Immunity
Ali Bani-Fatemi, Richie Jeremian, Kevin Z Wang, Jose Silveira, Clement Zai, Nathan J Kolla, Ariel Graff, Philip Gerretsen, John Strauss, Vincenzo De Luca
Schizophrenia is a major clinical problem and represents a major risk factor for suicide. The molecular mechanisms of suicidal behavior in psychosis remain poorly investigated, although it has been hypothesized that epigenetic processes are involved in the etiology of both psychosis and suicidality. In this study, epigenome-wide patterns of methylation were measured in schizophrenia suicide attempters (n = 54) and schizophrenia non-suicide attempters (n = 69) using DNA extracted from white blood cells (WBC)...
July 20, 2018: Journal of Psychiatric Research
James A Chamberlain, Pierre-Antoine Dugué, Julie K Bassett, Allison M Hodge, Maree T Brinkman, JiHoon E Joo, Chol-Hee Jung, Enes Makalic, Daniel F Schmidt, John L Hopper, Daniel D Buchanan, Dallas R English, Melissa C Southey, Graham G Giles, Roger L Milne
Background: Folate and other one-carbon metabolism nutrients are essential to enable DNA methylation to occur, but the extent to which their dietary intake influences methylation in adulthood is unclear. Objective: We assessed associations between dietary intake of these nutrients and DNA methylation in peripheral blood, overall and at specific genomic locations. Design: We conducted a cross-sectional study using baseline data and samples from 5186 adult participants in the Melbourne Collaborative Cohort Study (MCCS)...
August 8, 2018: American Journal of Clinical Nutrition
Xiaowu Chen, Yudong He, Zhipeng Wang, Jun Li
Cytochrome P450 aromatase (P450arom), which is encoded by cyp19a1a, can convert androgen to estrogen. Therefore, P450arom is important in gonadal differentiation and maintenance. In this study, we analyzed the expression and DNA methylation of cyp19a from Chinese sea perch Lateolabrax maculatus (sp. cyp19a1a). The sp. cyp19a1a gene consists of 9 exons, but only 3.5 kb, being smaller than the human cyp19a1a, as a result of small introns. The sp. cyp19a1a protein contains 518 amino acid residues and evolutionarily conserved domains and is clustered in the teleost subfamily on the phylogenetic tree...
August 9, 2018: Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology
Marie-Pierre Belot, Anne-Laure Castell, Sophie Le Fur, Pierre Bougnères
IL2RA, a subunit of the high affinity receptor for interleukin-2 (IL2), plays a crucial role in immune homeostasis. Notably, IL2RA expression is induced in CD4+ T cells in response to various stimuli and is constitutive in regulatory T cells (Tregs). We selected for our study 18 CpGs located within cognate regulatory regions of the IL2RA locus and characterized their methylation in naive, regulatory, and memory CD4+ T cells. We found that 5/18 CpGs (notably CpG + 3502) show dynamic, active demethylation during the in vitro activation of naive CD4+ T cells...
August 10, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Cristiana Lo Nigro, Daniela Vivenza, Nerina Denaro, Laura Lattanzio, Mirella Fortunato, Tim Crook, Marco Carlo Merlano
Background: Biomarkers predictive of response to chemoradiotherapy (CRT) regimens for locally advanced head and neck squamous cell carcinoma (LA-HNSCC) are urgently required to identify patients in whom this approach is likely to be effective. TP53 mutations and epidermal growth factor (EGFR) overexpression are common markers of disease. Dual-specificity-phosphatase-2 (DUSP2) has an essential role in cell proliferation, cancer and immune responses. Methods: Aberrant DUSP2 methylation was investigated by pyrosequencing in 5 HNSCC cell lines, 112 LA-HNSCC tumours...
July 2018: Annals of Translational Medicine
Aditi Chandra, Swapan Senapati, Sudipta Roy, Gobinda Chatterjee, Raghunath Chatterjee
BACKGROUND: Psoriasis is a chronic inflammatory autoimmune skin disorder. Several studies suggested psoriasis to be a complex multifactorial disease, but the exact triggering factor is yet to be determined. Evidences suggest that in addition to genetic factors, epigenetic reprogramming is also involved in psoriasis development. Major histopathological features, like increased proliferation and abnormal differentiation of keratinocytes, and immune cell infiltrations are characteristic marks of psoriatic skin lesions...
August 9, 2018: Clinical Epigenetics
Xue Zhang, Xiaoting Chen, Matthew T Weirauch, Xiang Zhang, J D Burleson, Eric B Brandt, Hong Ji
Exposures to diesel exhaust particles (DEP) from traffic and house dust mite (HDM) allergens significantly increase risks of airway diseases, including asthma. This negative impact of DEP and HDM may in part be mediated by epigenetic mechanisms. Beyond functioning as a mechanical barrier, airway epithelial cells provide the first line of immune defense towards DEP and HDM exposures. To understand the epigenetic responses of airway epithelial cells to these exposures, we exposed human bronchial epithelial cells to DEP and HDM and studied genome-wide 5-methyl-cytosine (5mC) and 5-hydroxy-methylcytosine (5hmC) at base resolution...
July 2018: Environmental Epigenetics
Soon Young Kim, Tae Il Kim
In the past two decades, besides conventional adenoma pathway, a subset of colonic lesions, including hyperplastic polyps, sessile serrated adenoma/polyps, and traditional serrated adenomas have been suggested as precancerous lesions via the alternative serrated neoplasia pathway. Major molecular alterations of sessile serrated neoplasia include BRAF mutation, high CpG island methylator phenotype, and escape of cellular senescence and progression via methylation of tumor suppressor genes or mismatch repair genes...
July 2018: Intestinal Research
Takashi Murakami, Naoto Sakamoto, Akihito Nagahara
Sessile serrated adenoma/polyps (SSA/Ps) are early precursor lesions in the serrated neoplasia pathway, which results in colorectal carcinomas with BRAF mutations, methylation for DNA repair genes, a CpG island methylator phenotype, and high levels of microsatellite instability. Some of these lesions can rapidly become dysplastic or invasive carcinomas that exhibit high lymphatic invasion and lymph node metastasis potentials. Detecting serrated lesions, including SSA/Ps with and without dysplasia/carcinoma, is critical, but SSA/Ps can be difficult to detect, are inconsistently identified by endoscopists and pathologists, and are often incompletely resected...
August 7, 2018: World Journal of Gastroenterology: WJG
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