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Alexa B R McIntyre, Noah Alexander, Kirill Grigorev, Daniela Bezdan, Heike Sichtig, Charles Y Chiu, Christopher E Mason
The DNA base modification N6-methyladenine (m6 A) is involved in many pathways related to the survival of bacteria and their interactions with hosts. Nanopore sequencing offers a new, portable method to detect base modifications. Here, we show that a neural network can improve m6 A detection at trained sequence contexts compared to previously published methods using deviations between measured and expected current values as each adenine travels through a pore. The model, implemented as the mCaller software package, can be extended to detect known or confirm suspected methyltransferase target motifs based on predictions of methylation at untrained contexts...
February 4, 2019: Nature Communications
Dan Xiang, Jiawei Xiao, Linyan Fu, Lihua Yao, Qirong Wan, Ling Xiao, Fan Zhu, Gaohua Wang, Zhongchun Liu
Tacr2, the gene encoding the NK2 receptor, belongs to G protein-coupled receptors. Accumulating evidence has indicated that the tachykinin receptors may contribute to the pathophysiology of depression. During the last decade, some studies have shown that Tacr2 activation is involved in the modulation of emotional processes. However, the extent, to which stress impacts Tacr2 expression remains unclear. The molecular mechanisms underlying depression also remain poorly understood. In this study, we subjected adult male Sprague Dawley (SD) rats to chronic unpredictable mild stress (CUMS) to induce a depression-like phenotype...
January 31, 2019: Behavioural Brain Research
Shiyu Tao, Tianjiao Zhou, Perot Saelao, Ying Wang, Yuhua Zhu, Tiantian Li, Huaijun Zhou, Junjun Wang
Intrauterine growth restriction (IUGR) remains a major problem in swine production since the associated low birth weight leads to high rates of pre-weaning morbidity and mortality, and permanent retardation of growth and development. The underlying regulatory mechanisms from the aspects of epigenetic modification receive widespread attention. Studies explore the changes in genome wide methylation in small intestine (SI), liver and longissimus dorsi muscle (LDM) between IUGR and normal birth weight (NBW) newborn piglets using a methylated DNA immunoprecipitation-sequencing (MeDIP-Seq) approach...
January 24, 2019: Current Protein & Peptide Science
Yan Zhu, Zhenning Cao, Chang Lu
Studies of dynamic epigenomic changes during tumorigenesis using mice often require profiling epigenomes using a tiny quantity of tissue samples. Conventional epigenomic tests do not support such analysis due to the large amount of materials required by these assays. In this study, we developed an ultrasensitive microfluidics-based methylated DNA immunoprecipitation followed by next-generation sequencing (MeDIP-seq) technology for profiling methylomes using as little as 0.5 ng DNA (or ∼100 cells) with 1.5 h on-chip process for immunoprecipitation...
January 11, 2019: Analyst
Jingting Xu, Shimeng Liu, Ping Yin, Serdar Bulun, Yang Dai
BACKGROUND: DNA methylation of CpG dinucleotides is an essential epigenetic modification that plays a key role in transcription. Widely used DNA enrichment-based methods offer high coverage for measuring methylated CpG dinucleotides, with the lowest cost per CpG covered genome-wide. However, these methods measure the DNA enrichment of methyl-CpG binding, and thus do not provide information on absolute methylation levels. Further, the enrichment is influenced by various confounding factors in addition to methylation status, for example, CpG density...
December 22, 2018: BMC Bioinformatics
Madeline Rose Keleher, Rabab Zaidi, Lauren Hicks, Shyam Shah, Xiaoyun Xing, Daofeng Li, Ting Wang, James M Cheverud
BACKGROUND: While the genetics of obesity has been well defined, the epigenetics of obesity is poorly understood. Here, we used a genome-wide approach to identify genes with differences in both DNA methylation and expression associated with a high-fat diet in mice. RESULTS: We weaned genetically identical Small (SM/J) mice onto a high-fat or low-fat diet and measured their weights weekly, tested their glucose and insulin tolerance, assessed serum biomarkers, and weighed their organs at necropsy...
December 7, 2018: BMC Genomics
Hongyu Zhang, Asif Ali, Feixue Hou, Tingkai Wu, Daiming Guo, Xiufeng Zeng, Fangfang Wang, Huixia Zhao, Xiaoqiong Chen, Peizhou Xu, Xianjun Wu
BACKGROUND: Polyploidy, or whole-genome duplication (WGD) promotes genetic diversification in plants. However, whether WGD is accompanied by epigenetic regulation especially DNA methylation remains yet elusive. Methylation of different region in genomic DNA play discrete role in gene regulation and developmental processes in plants. RESULTS: In our study, we used an apomictic rice line (SARII-628) that produces twin seedlings of different ploidy for methylated DNA immunoprecipitation sequencing (MeDIP-seq)...
November 29, 2018: BMC Plant Biology
Han Chen, Haidong Shu, Liyuan Wang, Fan Zhang, Xi Li, Sylvans Ochieng Ochola, Fei Mao, Hongyu Ma, Wenwu Ye, Tingting Gu, Lubin Jiang, Yufeng Wu, Yuanchao Wang, Sophien Kamoun, Suomeng Dong
BACKGROUND: Filamentous plant pathogen genomes often display a bipartite architecture with gene-sparse, repeat-rich compartments serving as a cradle for adaptive evolution. The extent to which this two-speed genome architecture is associated with genome-wide DNA modifications is unknown. RESULTS: We show that the oomycetes Phytophthora infestans and Phytophthora sojae possess functional adenine N6-methylation (6mA) methyltransferases that modulate patterns of 6mA marks across the genome...
October 31, 2018: Genome Biology
Genliang Li, Hui Qian
To investigate the possible effects of epigenetic modification of testis protein-encoding genes on precocious puberty of Eriocheir sinensis, we used MeDIP-seq and hMeDIP-seq techniques to compare the methylation and hydroxymethylation of 263 E. sinensis protein-encoding genes known in the NCBI database in precocious testes with those in normally developing testes. The results showed that total methylation level of those genes was lower than their total hydroxymethylation level. Moreover, their total hydroxymethylation level in precocious testes was significantly lower than that in normal testes...
January 30, 2019: Gene
Chad D Dechow, Wan-Sheng Liu
BACKGROUND: Milk yield for Holstein cows has doubled over five decades due to genetic selection and changes to management, but the molecular mechanisms that facilitated this increase are mostly unknown. Epigenetic modifications to the cattle genome are a plausible molecular mechanism to cause variation in milk yield and our objective was to describe genome-wide DNA methylation patterns in peripheral blood mononuclear cells (PBMC) from mature Holstein dairy cows with variable milk yield...
October 11, 2018: BMC Genomics
Xin Sun, Justin C St John
BACKGROUND: There are multiple copies of mitochondrial DNA (mtDNA) present in each cell type, and they are strictly regulated in a cell-specific manner by a group of nuclear-encoded mtDNA-specific replication factors. This strict regulation of mtDNA copy number is mediated by cell-specific DNA methylation of these replication factors. Glioblastoma multiforme, HSR-GBM1, cells are hyper-methylated and maintain low mtDNA copy number to support their tumorigenic status. We have previously shown that when HSR-GBM1 cells with 50% of their original mtDNA content were inoculated into mice, tumours grew more aggressively than non-depleted cells...
September 12, 2018: Epigenetics & Chromatin
Hua Liu, Jianjiao Li, Ying Yang, Liu Liu, Lifu Yu, Minsong Tu, Ruihong Yuan, Wanyuan Yue, Qi Luo, Yonghua Ruan, Xiaoming Dai
To identify potential biomarkers of lingual cancer, 75 female C57BL/6J mice were subjected to 16-week oral delivery of 4-nitroquinoline-1-oxide (4NQO; 50 mg/L), with 10 mice used as controls. Lingual mucosa samples representative of normal tissue (week 0) and early (week 12) and advanced (week 28) tumorigenesis were harvested for microarray and methylated DNA immunoprecipitation sequencing (MeDIP-Seq). Combined analysis with Short Time-series Expression Miner (STEM), the Cytoscape plugin cytoHubba, and screening of differentially expressed genes enabled identification of 63 hub genes predominantly altered in the early stage rather than the advanced stage...
August 22, 2018: Scientific Reports
Yan Zhou, Jiadi Zhu, Mingtao Zhao, Baoxue Zhang, Chunfu Jiang, Xiyan Yang
DNA methylation is an essential epigenetic modification involved in regulating the expression of mammalian genomes. A variety of experimental approaches to generate genome-wide or whole-genome DNA methylation data have emerged in recent years. Methylated DNA immunoprecipitation followed by sequencing (MeDIP-seq) is one of the major tools used in whole-genome epigenetic studies. However, analyzing this data in terms of accuracy, sensitivity, and speed still remains an important challenge. Existing methods, such as BATMAN and MEDIPS, analyze MeDIP-seq data by dividing the whole genome into equal length windows and assume that each CpG of the same window has the same methylation level...
2018: PloS One
Gregory Livshits, Ida Malkin, Ruth C E Bowyer, Serena Verdi, Jordana T Bell, Cristina Menni, Frances M K Williams, Claire J Steves
Chronic widespread musculoskeletal pain (CWP) and frailty are prevalent conditions in older people. We have shown previously that interindividual variation in frailty and CWP is genetically determined. We also reported an association of frailty and CWP caused by shared genetic and common environmental factors. The aim of this study was to use omic approaches to identify molecular genetic factors underlying the heritability of frailty and its genetic correlation with CWP. Frailty was quantified through the Rockwood Frailty Index (FI) as a proportion of deficits from 33 binary health deficit questions in 3626 female twins...
October 25, 2018: Pain
Sabrina Grasse, Matthias Lienhard, Steffen Frese, Martin Kerick, Anne Steinbach, Christina Grimm, Michelle Hussong, Jana Rolff, Michael Becker, Felix Dreher, Uwe Schirmer, Stefan Boerno, Anna Ramisch, Gunda Leschber, Bernd Timmermann, Christian Grohé, Heike Lüders, Martin Vingron, Iduna Fichtner, Sebastian Klein, Margarete Odenthal, Reinhard Büttner, Hans Lehrach, Holger Sültmann, Ralf Herwig, Michal R Schweiger
BACKGROUND: Non-small cell lung cancer (NSCLC) is the most common cause of cancer-related deaths worldwide and is primarily treated with radiation, surgery, and platinum-based drugs like cisplatin and carboplatin. The major challenge in the treatment of NSCLC patients is intrinsic or acquired resistance to chemotherapy. Molecular markers predicting the outcome of the patients are urgently needed. METHODS: Here, we employed patient-derived xenografts (PDXs) to detect predictive methylation biomarkers for platin-based therapies...
July 20, 2018: Genome Medicine
Wei Li, Renqiao Tang, Feifei Ma, Shengrong Ouyang, Zhuo Liu, Jianxin Wu
Folic acid (FA) supplementation may protect from obesity and insulin resistance, the effects and mechanism of FA on chronic high-fat-diet-induced obesity-related metabolic disorders are not well elucidated. We adopted a genome-wide approach to directly examine whether FA supplementation affects the DNA methylation profile of mouse adipose tissue and identify the functional consequences of these changes. Mice were fed a high-fat diet (HFD), normal diet (ND) or an HFD supplemented with folic acid (20 μg/ml in drinking water) for 10 weeks, epididymal fat was harvested, and genome-wide DNA methylation analyses were performed using methylated DNA immunoprecipitation sequencing (MeDIP-seq)...
September 2018: Journal of Nutritional Biochemistry
Kathryn Miranda, Xiaoming Yang, Marpe Bam, E Angela Murphy, Prakash S Nagarkatti, Mitzi Nagarkatti
BACKGROUND/OBJECTIVES: Obesity is a pandemic disorder that is characterized by accumulation of adipose tissue and chronic low-grade inflammation that is driven primarily by adipose tissue macrophages (ATMs). While ATM polarization from pro-(M1) to anti-(M2) inflammatory phenotype influences insulin sensitivity and energy expenditure, the mechanisms of such a switch are unclear. In the current study, we identified epigenetic pathways including microRNAs (miR) in ATMs that regulate obesity-induced inflammation...
June 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
Xiaolong Zhou, Songbai Yang, Feifei Yan, Ke He, Ayong Zhao
DNA methylation is an important epigenetic modification involved in the estrous cycle and the regulation of reproduction. Here, we investigated the genome-wide profiles of DNA methylation in porcine ovaries in proestrus and estrus using methylated DNA immunoprecipitation sequencing. The results showed that DNA methylation was enriched in intergenic and intron regions. The methylation levels of coding regions were higher than those of the 5'- and 3'-flanking regions of genes. There were 4,813 differentially methylated regions (DMRs) of CpG islands in the estrus vs...
September 1, 2018: Physiological Genomics
Qing-Bing Zhou, Li-Qi Wu, Yin Zhang, Zhi-Fang Zhang, Feng-Qin Xu
OBJECTIVE: To investigate the effects of Zhizi Chuanxiong Capsule (ZCC, ) on abnormal DNA methylation in a rabbit model of atherosclerosis (AS). METHODS: After 1 week of adaptive feeding, 48 New Zealand white rabbits were randomly divided into 4 groups: a control group (n=12) fed with normal diet for 22 weeks; a model group (n=12) fed with high fat diet for 14 weeks followed by 8 weeks of normal diet feeding; a low-dose ZCC group (n=12) fed with high fat diet and low-dose ZCC for 14 weeks, followed by 8 weeks of normal diet and low-dose drug; a high-dose ZCC group (n=12) fed with high fat diet and high-dose drug for 14 weeks, followed by 8 weeks of normal diet and high-dose drug...
May 11, 2018: Chinese Journal of Integrative Medicine
Fugui Zhu, Qianshu Zhu, Dan Ye, Qingquan Zhang, Yiwei Yang, Xudong Guo, Zhenping Liu, Zeyidan Jiapaer, Xiaoping Wan, Guiying Wang, Wen Chen, Songcheng Zhu, Cizhong Jiang, Weiyang Shi, Jiuhong Kang
Sin3a is a core component of histone-deacetylation-activity-associated transcriptional repressor complex, playing important roles in early embryo development. Here, we reported that down-regulation of Sin3a led to the loss of embryonic stem cell (ESC) self-renewal and skewed differentiation into mesendoderm lineage. We found that Sin3a functioned as a transcriptional coactivator of the critical Nodal antagonist Lefty1 through interacting with Tet1 to de-methylate the Lefty1 promoter. Further studies showed that two amino acid residues (Phe147, Phe182) in the PAH1 domain of Sin3a are essential for Sin3a-Tet1 interaction and its activity in regulating pluripotency...
July 6, 2018: Nucleic Acids Research
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