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Yanting Luo, Jianlin He, Xiguang Xu, Ming-An Sun, Xiaowei Wu, Xuemei Lu, Hehuang Xie
Embryonic stem cells (ESCs) consist of a population of self-renewing cells displaying extensive phenotypic and functional heterogeneity. Research towards the understanding of the epigenetic mechanisms underlying the heterogeneity among ESCs is still in its initial stage. Key issues, such as how to identify cell-subset specifically methylated loci and how to interpret the biological meanings of methylation variations remain largely unexplored. To fill in the research gap, we implemented a computational pipeline to analyze single-cell methylome and to perform an integrative analysis with single-cell transcriptome data...
March 2018: PLoS Computational Biology
Yuet-Kin Leung, Bin Ouyang, Liang Niu, Changchun Xie, Jun Ying, Mario Medvedovic, Aimin Chen, Pal Weihe, Damaskini Valvi, Philippe Grandjean, Shuk-Mei Ho
Faroe islanders consume marine foods contaminated with methylmercury (MeHg), polychlorinated biphenyls (PCBs), and other toxicants associated with chronic disease risks. Differential DNA methylation at specific CpG sites in cord blood may serve as a surrogate biomarker of health impacts from chemical exposures. We aimed to identify key environmental chemicals in cord blood associated with DNA methylation changes in a population with elevated exposure to chemical mixtures. We studied 72 participants of a Faroese birth cohort recruited between 1986 and 1987 and followed until adulthood...
March 21, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Quentin Gouil, David C Baulcombe
BACKGROUND: Freakish and rare or the tip of the iceberg? Both phrases have been used to refer to paramutation, an epigenetic drive that contravenes Mendel's first law of segregation. Although its underlying mechanisms are beginning to unravel, its understanding relies only on a few examples that may involve transgenes or artificially generated epialleles. RESULTS: By using DNA methylation of introgression lines as an indication of past paramutation, we reveal that the paramutation-like properties of the H06 locus in hybrids of Solanum lycopersicum and a range of tomato relatives and cultivars depend on the timing of sRNA production and conform to an RNA-directed mechanism...
March 20, 2018: BMC Genomics
J Richard Pilsner, Alex Shershebnev, Yulia Medvedeva, Alexander Suvorov, Haotian Wu, Andrey Goltsov, Evgeny Loukianov, Tatiana Andreeva, Fedor Gusev, Andrey Manakhov, Luidmila Smigulina, Maria Logacheva, Victoria Shtratnikova, Irina Kuznetsova, Peter Speranskiy-Podobed, Jane S Burns, Paige L Williams, Susan Korrick, Mary M Lee, Evgeny Rogaev, Russ Hauser, Oleg Sergeyev
BACKGROUND: The association of exposure to endocrine disrupting chemicals in the peripubertal period with subsequent sperm DNA methylation is unknown. OBJECTIVE: We examined the association of peripubertal serum 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) concentrations with whole-genome bisulfite sequencing (WGBS) of sperm collected in young adulthood. METHODS: The Russian Children's Study is a prospective cohort of 516 boys who were enrolled at 8-9 years of age and provided semen samples at 18-19 years of age...
March 14, 2018: Reproductive Toxicology
Yue Guo, Renyi Wu, John M Gaspar, Davit Sargsyan, Zheng-Yuan Su, Chengyue Zhang, Linbo Gao, David Cheng, Wenji Li, Chao Wang, Ran Yin, Mingzhu Fang, Michael P Verzi, Ronald P Hart, Ah-Ng Kong
Inflammation is highly associated with colon carcinogenesis. Epigenetic mechanisms could play an important role in the initiation and progression of colon cancer. Curcumin, a dietary phytochemical, shows promising effects in suppressing colitis-associated colon cancer in AOM-DSS mice. However, the potential epigenetic mechanisms of curcumin in colon cancer remain unknown. In this study, the anti-cancer effect of curcumin in suppressing colon cancer in an 18-week AOM-DSS colon cancer mouse model was confirmed...
March 14, 2018: Carcinogenesis
Graziela de Sá Machado Araújo, Ronaldo da Silva Francisco Junior, Cristina Dos Santos Ferreira, Pedro Thyago Mozer Rodrigues, Douglas Terra Machado, Thais Louvain de Souza, Jozimara Teixeira de Souza, Cleiton Figueiredo Osorio da Silva, Antônio Francisco Alves da Silva, Claudia Caixeta Franco Andrade, Alan Tardin da Silva, Victor Ramos, Ana Beatriz Garcia, Filipe Brum Machado, Enrique Medina-Acosta
A hallmark of imprinted genes in mammals is the occurrence of parent-of-origin-dependent asymmetry of DNA cytosine methylation (5m C) of alleles at CpG islands (CGIs) in their promoter regions. This 5m CpG asymmetry between the parental alleles creates allele-specific imprinted differentially methylated regions (iDMRs). iDMRs are often coupled to the transcriptional repression of the methylated allele and the activation of the unmethylated allele in a tissue-specific, developmental-stage-specific and/or isoform-specific fashion...
2018: Frontiers in Genetics
Magali Kernaleguen, Christian Daviaud, Yimin Shen, Eric Bonnet, Victor Renault, Jean-François Deleuze, Florence Mauger, Jörg Tost
The analysis of genome-wide epigenomic alterations including DNA methylation and hydroxymethylation has become a subject of intensive research for many biological and disease-associated investigations. Whole-genome bisulfite sequencing (WGBS) using next-generation sequencing technologies is currently considered as the gold standard for a comprehensive and quantitative analysis of DNA methylation throughout the genome. However, bisulfite conversion does not allow distinguishing between cytosine methylation and hydroxymethylation requiring an additional chemical or enzymatic step to identify hydroxymethylated cytosines...
2018: Methods in Molecular Biology
Dulce B Vargas-Landin, Jahnvi Pflüger, Ryan Lister
Whole genome bisulfite sequencing (WGBS) enables the detection of DNA methylation at single base-pair resolution. The treatment of DNA with sodium bisulfite allows the discrimination of methylated and unmethylated cytosines, but the power of this technology can be limited by the input amounts of DNA and the length of DNA fragments due to DNA damage caused by the desulfonation process. Here, we describe a WGBS library preparation protocol that minimizes the loss and damage of DNA, generating high quality libraries amplified with fewer PCR cycles, and hence data with fewer PCR duplicates, from lower amounts of input material...
2018: Methods in Molecular Biology
Yan Zhang, Kai-Uwe Saum, Ben Schöttker, Bernd Holleczek, Hermann Brenner
Survival predictors are of potential use for informing on biological age and targeting prevention of aging-related morbidity. We assessed associations of 2 novel methylomic survival indicators, a methylation-based mortality risk score (MRscore) and the epigenetic clock-derived age acceleration (AA), with a well-known survival predictor, frailty index (FI), and compared the 3 indicators in mortality prediction. In a large population-based cohort with 14-year follow-up, we found both MRscore and AA to be independently associated with FI, but the association was much stronger for MRscore than for AA...
March 6, 2018: Aging
Zhenghao Li, Hisanori Takenobu, Amallia Nuggetsiana Setyawati, Nobuhiro Akita, Masayuki Haruta, Shunpei Satoh, Yoshitaka Shinno, Koji Chikaraishi, Kyosuke Mukae, Jesmin Akter, Ryuichi P Sugino, Atsuko Nakazawa, Akira Nakagawara, Hiroyuki Aburatani, Miki Ohira, Takehiko Kamijo
The polycomb repressor complex 2 molecule EZH2 is now known to play a role in essential cellular processes, namely, cell fate decisions, cell cycle regulation, senescence, cell differentiation, and cancer development/progression. EZH2 inhibitors have recently been developed; however, their effectiveness and underlying molecular mechanisms in many malignancies have not yet been elucidated in detail. Although the functional role of EZH2 in tumorigenesis in neuroblastoma (NB) has been investigated, mutations of EZH2 have not been reported...
March 6, 2018: Oncogene
Yang Wu, Jian Zeng, Futao Zhang, Zhihong Zhu, Ting Qi, Zhili Zheng, Luke R Lloyd-Jones, Riccardo E Marioni, Nicholas G Martin, Grant W Montgomery, Ian J Deary, Naomi R Wray, Peter M Visscher, Allan F McRae, Jian Yang
The identification of genes and regulatory elements underlying the associations discovered by GWAS is essential to understanding the aetiology of complex traits (including diseases). Here, we demonstrate an analytical paradigm of prioritizing genes and regulatory elements at GWAS loci for follow-up functional studies. We perform an integrative analysis that uses summary-level SNP data from multi-omics studies to detect DNA methylation (DNAm) sites associated with gene expression and phenotype through shared genetic effects (i...
March 2, 2018: Nature Communications
Lexiang Ji, William T Jordan, Xiuling Shi, Lulu Hu, Chuan He, Robert J Schmitz
DNA methylation in the promoters of plant genes sometimes leads to transcriptional repression, and the loss of DNA methylation in methyltransferase mutants results in altered gene expression and severe developmental defects. However, many cases of naturally occurring DNA methylation variations have been reported, whereby altered expression of differentially methylated genes is responsible for agronomically important traits. The ability to manipulate plant methylomes to generate epigenetically distinct individuals could be invaluable for breeding and research purposes...
March 1, 2018: Nature Communications
Matthew Ouellette, J Peter Gogarten, Jessica Lajoie, Andrea M Makkay, R Thane Papke
DNA methyltransferases (MTases), which catalyze the methylation of adenine and cytosine bases in DNA, can occur in bacteria and archaea alongside cognate restriction endonucleases (REases) in restriction-modification (RM) systems or independently as orphan MTases. Although DNA methylation and MTases have been well-characterized in bacteria, research into archaeal MTases has been limited. A previous study examined the genomic DNA methylation patterns (methylome) of the halophilic archaeon Haloferax volcanii , a model archaeal system which can be easily manipulated in laboratory settings, via single-molecule real-time (SMRT) sequencing and deletion of a putative MTase gene ( HVO_A0006 )...
February 27, 2018: Genes
Dirk Walter, Patrick N Harter, Florian Battke, Ria Winkelmann, Markus Schneider, Katharina Holzer, Christine Koch, Jörg Bojunga, Stefan Zeuzem, Martin Leo Hansmann, Jan Peveling-Oberhag, Oliver Waidmann
Data on intratumoral heterogeneity of small intestine neuroendocrine tumors (SI-NETs) and related liver metastasis are limited. The aim of this study was to characterize genetic heterogeneity of 5 patients with SI-NETs. Therefore, formalin-fixed, paraffin-embedded tissue samples of primary and metastatic lesions as well as benign liver of five patients with synchronously metastasized, well differentiated SI-NETs were analyzed with whole exome sequencing. For one patient, chip based 850k whole DNA methylome analysis was performed of primary and metastatic tumor tissue as well as control tissue...
February 28, 2018: Scientific Reports
P S Zeiner, J Zinke, D J Kowalewski, S Bernatz, J Tichy, M W Ronellenfitsch, F Thorsen, A Berger, M T Forster, A Muller, J P Steinbach, R Beschorner, J Wischhusen, H M Kvasnicka, K H Plate, S Stefanović, B Weide, M Mittelbronn, P N Harter
Despite multidisciplinary local and systemic therapeutic approaches, the prognosis for most patients with brain metastases is still dismal. The role of adaptive and innate anti-tumor response including the Human Leukocyte Antigen (HLA) machinery of antigen presentation is still unclear. We present data on the HLA class II-chaperone molecule CD74 in brain metastases and its impact on the HLA peptidome complexity.We analyzed CD74 and HLA class II expression on tumor cells in a subset of 236 human brain metastases, primary tumors and peripheral metastases of different entities in association with clinical data including overall survival...
March 1, 2018: Acta Neuropathologica Communications
Xinxia Wang, Baofa Sun, Qin Jiang, Ruifan Wu, Min Cai, Yongxi Yao, Qing Liu, Hailing Shi, Jie Feng, Yizhen Wang
BACKGROUND/OBJECTIVE: N6 -methyladenosine (m6 A) modification of mRNA plays an important role in regulating adipogenesis. However, its underlying mechanism remains largely unknown. SUBJECTS/METHODS: Using Jinhua and Landrace pigs as fat and lean models, we presented a comprehensive transcriptome-wide m6 A profiling in adipose tissues from these two pig breeds. Two differentially methylated genes were selected to explore the mechanisms of m6 A-mediated regulation of gene function...
February 27, 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
Gunter Vogt
In the last 15 years, considerable attempts have been undertaken to develop the obligately parthenogenetic marbled crayfish Procambarus virginalis as a new model in biology. Its main advantage is the production of large numbers of offspring that are genetically identical to the mother, making this crustacean particularly suitable for research in epigenetics. Now, a draft genome, transcriptome and genome-wide methylome are available opening new windows for research. In this article, I summarize the biological advantages and genomic and epigenetic features of marbled crayfish and, based on first promising data, discuss what this new model could contribute to answering of ''big'' biological questions...
March 2018: Journal of Biosciences
Guochao Li, Dong Wang, Wencui Ma, Ke An, Zongzhi Liu, Xinyu Wang, Caiyun Yang, Fengxia Du, Xiao Han, Shuang Chang, Hui Yu, Zilong Zhang, Zitong Zhao, Yan Zhang, Junyun Wang, Yingli Sun
AIM: Cancer stem cells (CSCs) drive triple-negative breast cancer recurrence via their properties of self-renewal, invasiveness and radio/chemotherapy resistance. This study examined how CSCs might sustain these properties. MATERIALS & METHODS: Transcriptomes, DNA methylomes and histone modifications were compared between CSCs and non-CSCs. RESULTS: Transcriptome analysis revealed several pathways that were activated in CSCs, whereas cell cycle regulation pathways were inhibited...
February 26, 2018: Epigenomics
Agatha Schlüter, Juan Sandoval, Stéphane Fourcade, Angel Díaz-Lagares, Montserrat Ruiz, Patrizia Casaccia, Manel Esteller, Aurora Pujol
Epigenomic changes may either cause disease or modulate its expressivity, adding a layer of complexity to mendelian diseases. X-linked adrenoleukodystrophy (X-ALD) is a rare neurometabolic condition exhibiting discordant phenotypes, ranging from a childhood cerebral inflammatory demyelination (cALD) to an adult-onset mild axonopathy in spinal cords (AMN). The AMN form may occur with superimposed inflammatory brain demyelination (cAMN). All patients harbor loss of function mutations in the ABCD1 peroxisomal transporter of very-long chain fatty acids...
February 24, 2018: Brain Pathology
Anne Jouinot, Jerome Bertherat
Adrenocortical carcinoma (ACC) is a rare malignancy with a poor prognosis, the five-years overall survival being below 40%. However there is great variability of outcomes and we have now a better view of the heterogeneity of tumor aggressiveness. The extent of the disease at the time of diagnosis, best assayed by the European Network for the Study of Adrenal Tumors (ENSAT) staging score, is a major determinant of survival. The tumor grade, including the mitotic count and the Ki67 proliferation index, also appears as a strong prognostic factor...
February 23, 2018: European Journal of Endocrinology
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