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Epigenetics: Official Journal of the DNA Methylation Society

Ana Cheong, Sarah A Johnson, Emily C Howald, Mark R Ellersieck, Luísa Camacho, Sherry M Lewis, Michelle M Vanlandingham, Jun Ying, Shuk-Mei Ho, Cheryl S Rosenfeld
Bisphenol A (BPA), an endocrine disrupting chemical (EDC), is a ubiquitous pollutant. As part of the Consortium Linking Academic and Regulatory Insights on BPA Toxicity (CLARITY-BPA), we sought to determine whether exposure of Sprague-Dawley rats to 2,500 μg/kg/day BPA (BPA) or 0.5 μg/kg/day ethinyl estradiol (EE) from gestational day 6 through postnatal day 21 induces behavior-relevant gene expression and DNA methylation changes in hippocampus and hypothalamus at adulthood. RNA and DNA were isolated from both regions...
July 12, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Kelly J Brunst, Nicole Tignor, Allan Just, Zhonghua Liu, Xihong Lin, Michele R Hacker, Michelle Bosquet Enlow, Robert O Wright, Pei Wang, Andrea A Baccarelli, Rosalind J Wright
Evolving evidence links maternal stress exposure to changes in placental DNA methylation of specific genes regulating placental function that may have implications for the programming of a host of chronic disorders. Few studies have implemented an epigenome-wide approach. Using the Infinium HumanMethylation450 BeadChip (450K), we investigated epigenome-wide placental DNA methylation in relation to maternal experiences of traumatic and non-traumatic stressors over her lifetime assessed using the Life Stressor Checklist-Revised (LSC-R) survey (n = 207)...
July 12, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Boyang Zhang, Xiumei Hong, Hongkai Ji, Wan-Yee Tang, Mary Kimmel, Yuelong Ji, Colleen Pearson, Barry Zuckerman, Pamela J Surkan, Xiaobin Wang
Maternal smoking during pregnancy may affect newborn DNA methylation (DNAm). However, little is known about how these associations vary by a newborn's sex and/or maternal nutrition. To fill in this research gap, we investigated epigenome-wide DNAm associations with maternal smoking during pregnancy in African American mother-newborn pairs. DNAm profiling in cord (n=379) and maternal blood (n=300) were performed using the Illumina HumanMethylation450 BeadChip array. We identified 12 CpG sites whose DNAm levels in cord blood were associated with maternal smoking, at a false discovery rate <5%...
June 27, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Benjamin Hing, Patricia Braun, Zachary A Cordner, Erin R Ewald, Laura Moody, Melissa McKane, Virginia L Willour, Kellie L Tamashiro, James B Potash
Chronic stress resulting from prolonged exposure to negative life events increases the risk of mood and anxiety disorders. Although chronic stress can change gene expression relevant for behavior, molecular regulators of this change have not been fully determined. One process that could play a role is DNA methylation, an epigenetic process whereby a methyl group is added onto nucleotides, predominantly cytosine in the CpG context, and which can be induced by chronic stress. It is unknown to what extent chronic social defeat, a model of human social stress, influences DNA methylation patterns across the genome...
June 26, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Tao Wang, Matthew V Holt, Nicolas L Young
Histone posttranslational modifications (PTMs) help regulate DNA templated processes; however, relatively little work has unbiasedly explored the single-molecule combinations of histone PTMs, their dynamics on short timescales, or how these preexisting histone PTMs modulate further histone modifying enzyme activity. We use quantitative top down proteomics to unbiasedly measure histone H4 proteoforms (single-molecule combinations of PTMs) upon butyrate treatment. Our results show that histone proteoforms change in cells within 10 minutes of application of sodium butyrate...
June 25, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Xin Zhou, Zhibin Chen, Xiaodong Cai
Human tumors undergo massive changes in DNA methylation. Recent studies showed that site-specific methylation of CpG sites is determined by the DNA sequence context surrounding the CpG site, which alludes to a possible mechanism for site-specific aberrant DNA methylation in cancer through DNA-binding proteins. In this paper, DNA methylation data and RNA-Seq data of breast tumors and normal tissues in the database of The Cancer Genome Atlas (TCGA) were integrated with information of DNA motifs in seven databases to find DNA-binding proteins and their binding motifs that were involved in aberrant DNA methylation in breast cancer...
June 25, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Chongchang Zhou, Meng Ye, Shumin Ni, Qun Li, Dong Ye, Jinyun Li, Zhishen Shen, Hongxia Deng
DNA methylation plays an important role in the etiology and pathogenesis of head and neck squamous cell carcinoma (HNSCC). The current study aimed to identify aberrantly methylated-differentially expressed genes (DEGs) by a comprehensive bioinformatics analysis. In addition, we screened for DEGs affected by DNA methylation modification and further investigated their prognostic values for HNSCC. We included microarray data of DNA methylation (GSE25093 and GSE33202) and gene expression (GSE23036 and GSE58911) from Gene Expression Omnibus...
June 21, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Rajendra P Pangeni, Zhou Zhang, Angel A Alvarez, Xuechao Wan, Namratha Sastry, Songjian Lu, Taiping Shi, Tianzhi Huang, Charles X Lei, C David James, John A Kessler, Cameron W Brennan, Ichiro Nakano, Xinghua Lu, Bo Hu, Wei Zhang, Shi-Yuan Cheng
Glioma stem cells (GSCs), a subpopulation of tumor cells, contribute to tumor heterogeneity and therapy resistance. Gene expression profiling classified glioblastoma (GBM) and GSCs into four transcriptomically-defined subtypes. Here, we determined the DNA methylation signatures in transcriptomically pre-classified GSC and GBM bulk tumors subtypes. We hypothesized that these DNA methylation signatures correlate with gene expression and are uniquely associated either with only GSCs or only GBM bulk tumors. Additional methylation signatures may be commonly associated with both GSCs and GBM bulk tumors, i...
June 21, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Katarzyna Lubecka, Kirsty Flower, Megan Beetch, Jay Qiu, Lucinda Kurzava, Hannah Buvala, Adam Ruhayel, Samer Gawrieh, Suthat Liangpunsakul, Tracy Gonzalez, George McCabe, Naga Chalasani, James M Flanagan, Barbara Stefanska
Late onset of clinical symptoms in hepatocellular carcinoma (HCC) results in late diagnosis and poor disease outcome. Approximately 85% of individuals with HCC have underlying liver cirrhosis. However, not all cirrhotic patients develop cancer. Reliable tools that would distinguish cirrhotic patients who will develop cancer from those who will not are urgently needed. We used the Illumina HumanMethylation450 BeadChip microarray to test whether white blood cell DNA, an easily accessible source of DNA, exhibits site-specific changes in DNA methylation in blood of diagnosed HCC patients (post-diagnostic, 24 cases, 24 controls) and in prospectively collected blood specimens of HCC patients who were cancer-free at blood collection (pre-diagnostic, 21 cases, 21 controls)...
June 21, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Saadia Khilji, Munerah Hamed, Jihong Chen, Qiao Li
Molecular regulation of stem cell differentiation is exerted through both genetic and epigenetic determinants over distal regulatory or enhancer regions. Understanding the mechanistic action of active or poised enhancers is therefore imperative for control of stem cell differentiation. Based on the genome-wide co-occurrence of different epigenetic marks in committed proliferating myoblasts, we have previously generated a 14-state chromatin state model to profile rexinoid-responsive histone acetylation in early myoblast differentiation...
June 21, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Joy E Kirkpatrick, Keith L Kirkwood, Patrick M Woster
Periodontal disease (PD) afflicts 46% of Americans with no effective adjunctive therapies available. While most pharmacotherapy for PD targets bacteria, the host immune response is responsible for driving tissue damage and bone loss in severe disease. Herein, we establish that the histone demethylase KDM4B is a potential drug target for the treatment of PD. Immunohistochemical staining of diseased periodontal epithelium revealed an increased abundance of KDM4B that correlates with inflammation. In murine calvarial sections exposed to Aggregatibacter actinomycetemcomitans lipopolysaccharide (Aa-LPS), immunohistochemical staining revealed a significant increase in KDM4B protein expression...
June 21, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Jianchao Ying, Teng Xu, Qian Wang, Jun Ye, Jianxin Lyu
The accurate diagnosis of endometrial cancer (EC) holds great promise for improving its treatment choice and prognosis prediction. This work aimed to identify diagnostic biomarkers for differentiating EC tumors from tumors in other tissues, as well as prognostic signatures for predicting survival in EC patients. We identified 48 tissue-specific markers using a cohort of genome-wide methylation data from three common gynecological tumors and their corresponding normal tissues. A diagnostic classifier was constructed based on these 48 CpG markers that could predict cancerous versus normal tissue with an overall correct rate of 98...
June 18, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Chengchuang Song, Jian Wang, Yilei Ma, Zhaoxin Yang, Dong Dong, Hui Li, Jiameng Yang, Yongzhen Huang, Martin Plath, Yun Ma, Hong Chen
Long noncoding RNAs (lncRNAs) are involved in the regulation of skeletal muscle development. In the present study, differentially expressed lncRNAs were identified from RNA-seq data derived from myoblasts and myotubes. We conducted studies to elucidate the function and molecular mechanism of action of Linc-smad7 during skeletal muscle development. Our findings show that Linc-smad7 is upregulated during the early phase of myoblasts differentiation. In in vitro studies, we showed that overexpression of Linc-smad7 promoted the arrest of myoblasts in G1 phase, inhibited DNA replication, and induced myoblast differentiation...
June 18, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Judit Symmank, Cathrin Bayer, Christiane Schmidt, Anne Hahn, Daniel Pensold, Geraldine Zimmer
Epigenetic mechanisms of gene regulation, including DNA methylation and histone modifications, call increasing attention in the context of development and human health. Thereby, interactions between DNA methylating enzymes and histone modifications tremendously multiply the spectrum of potential regulatory functions. Epigenetic networks are critically involved in the establishment and functionality of neuronal circuits that are composed of gamma-aminobutyric acid (GABA)-positive inhibitory interneurons and excitatory principal neurons in the cerebral cortex...
June 18, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Shota Nishitani, Sasha E Parets, Brian W Haas, Alicia K Smith
Saliva is a non-invasive, easily accessible tissue, which is regularly collected in large epidemiological studies to examine genetic questions. Recently, it is becoming more common to use saliva to assess DNA methylation. However, DNA extracted from saliva is a mixture of both bacterial and human DNA derived from epithelial and immune cells in the mouth. Thus, there are unique challenges to using salivary DNA in methylation studies that can influence data quality. This study assesses: (1) quantification of human DNA after extraction; (2) delineation of human and bacterial DNA; (3) bisulfite conversion (BSC); (4) quantification of BSC DNA; (5) PCR amplification of BSC DNA from saliva and; (6) quantitation of DNA methylation with a targeted assay...
June 18, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Hagen Klett, Yesilda Balavarca, Reka Toth, Biljana Gigic, Nina Habermann, Dominique Scherer, Petra Schrotz-King, Alexis Ulrich, Peter Schirmacher, Esther Herpel, Hermann Brenner, Cornelia M Ulrich, Karin B Michels, Hauke Busch, Melanie Boerries
DNA methylation is recognized as one of several epigenetic regulators of gene expression and as potential driver of carcinogenesis through gene-silencing of tumor suppressors and activation of oncogenes. However, abnormal methylation, even of promoter regions, does not necessarily alter gene expression levels, especially if the gene is already silenced, leaving the exact mechanisms of methylation unanswered. Using a large cohort of matching DNA methylation and gene expression samples of colorectal cancer (CRC; n = 77) and normal adjacent mucosa tissues (n = 108), we investigated the regulatory role of methylation on gene expression...
May 3, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Na Young Choi, Jin Seok Bang, Hye Jeong Lee, Yo Seph Park, Minseong Lee, Dahee Jeong, Kisung Ko, Dong Wook Han, Hyung-Min Chung, Gwang Jun Kim, Seung-Hyuk Shim, Han Sung Hwang, Kinarm Ko
Genomic imprinting is the process of epigenetic modification whereby genes are expressed in a parent-of-origin dependent manner; it plays an important role in normal growth and development. Parthenogenetic embryos contain only the maternal genome. Parthenogenetic embryonic stem cells could be useful for studying imprinted genes. In humans, mature cystic ovarian teratomas originate from parthenogenetic activation of oocytes; they are composed of highly differentiated mature tissues containing all three germ layers...
May 3, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Baigalmaa Lkhagva, Yu-Hsun Kao, Ting-I Lee, Ting-Wei Lee, Wan-Li Cheng, Yi-Jen Chen
Histone deacetylases (HDACs) play vital roles in the pathophysiology of heart failure, which is associated with mitochondrial dysfunction. Tumor necrosis factor-α (TNF-α) contributes to the genesis of heart failure and impairs mitochondria. This study evaluated the role of HDACs in TNF-α-induced mitochondrial dysfunction and investigated their therapeutic potential and underlying mechanisms. We measured mitochondrial oxygen consumption rate (OCR) and ATP production using Seahorse XF24 extracellular flux analyzer and bioluminescent assay in control and TNF-α (10 ng/ml, 24 h)-treated HL-1 cells with or without HDAC inhibition...
May 3, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Andrew VonHandorf, Francisco Javier Sánchez-Martín, Jacek Biesiada, Hongxia Zhang, Xiang Zhang, Mario Medvedovic, Alvaro Puga
Hexavalent chromium compounds are well-established respiratory carcinogens used in industrial processes. While inhalation exposure constitutes an occupational risk affecting mostly chromium workers, environmental exposure from drinking water is a widespread gastrointestinal cancer risk, affecting millions of people throughout the world. Cr(VI) is genotoxic, forming protein-Cr-DNA adducts and silencing tumor suppressor genes, but its mechanism of action at the molecular level is poorly understood. Our prior work using FAIRE showed that Cr(VI) disrupted the binding of transcription factors CTCF and AP-1 to their cognate chromatin sites...
May 3, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Annie Vogel Ciernia, Benjamin I Laufer, Keith W Dunaway, Charles E Mordaunt, Rochelle L Coulson, Theresa S Totah, Danielle S Stolzenberg, Jaime C Frahm, Akanksha Singh-Taylor, Tallie Z Baram, Janine M LaSalle, Dag H Yasui
Augmented maternal care during the first postnatal week promotes life-long stress resilience and improved memory compared with the outcome of routine rearing conditions. Recent evidence suggests that this programming commences with altered synaptic connectivity of stress sensitive hypothalamic neurons. However, the epigenomic basis of the long-lived consequences is not well understood. Here, we employed whole-genome bisulfite sequencing (WGBS), RNA-sequencing (RNA-seq), and a multiplex microRNA (miRNA) assay to examine the effects of augmented maternal care on DNA cytosine methylation, gene expression, and miRNA expression...
2018: Epigenetics: Official Journal of the DNA Methylation Society
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