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Epigenetics: Official Journal of the DNA Methylation Society

Liesbeth Van Wesenbeeck, Leen Janssens, Hanne Meeuws, Ole Lagatie, Lieven Stuyver
Most tissue samples available for cancer research are archived as formalin-fixed paraffin-embedded (FFPE) samples. However, the fixation process and the long storage duration lead to DNA fragmentation and hinder epigenome analysis. The use of droplet digital PCR (ddPCR) to detect DNA methylation has recently emerged. In this study, we compare an optimized ddPCR assay with a conventional qPCR assay by targeting a dilution series of control DNA. In addition, we compare the ddPCR technology with results from Infinium arrays targeting two separate CpG sites on a set of colon adenoma FFPE samples...
March 12, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Di Ye, Li Zhang, Weidong Fan, Xianquan Zhang, Erbo Dong
Synthetic antidepressants in current use for the complex etiopathogeneses of depression have slow response and remission as well as various unpleasant side effects. As a result, it is imperative to develop new antidepressants with more effectiveness and less severe side effects. Recent studies demonstrated that genipin, the aglycon of geniposide, extracted from Gardenia jasminoides Ellis has antidepressive effects. However, knowledge regarding the molecular mechanisms of its antidepressant effects remains limited...
March 9, 2018: Epigenetics: Official Journal of the DNA Methylation Society
L Montrose, V Padmanabhan, J M Goodrich, S E Domino, M C Treadwell, J D Meeker, D J Watkins, D C Dolinoy
Endocrine disrupting chemicals (EDCs) pose a public health risk through disruption of normal biological processes. Identifying toxicoepigenetic mechanisms of developmental exposure-induced effects for EDCs, such as phthalates or bisphenol A (BPA), is essential. Here, we investigate whether maternal exposure to EDCs is predictive of infant DNA methylation at candidate gene regions. In the Michigan Mother-Infant Pairs (MMIP) cohort, DNA was extracted from cord blood leukocytes for methylation analysis by pyrosequencing (n = 116) and methylation changes related to first trimester levels of 9 phthalate metabolites and BPA...
March 7, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Carl Baribault, Kenneth C Ehrlich, V K Chaithanya Ponnaluri, Sriharsa Pradhan, Michelle Lacey, Melanie Ehrlich
DNA methylation can affect tissue-specific gene transcription in ways that are difficult to discern from studies focused on genome-wide analyses of differentially methylated regions (DMRs). To elucidate the variety of associations between differentiation-related DNA hypermethylation and transcription, we used available epigenomic and transcriptomic profiles from 38 human cell/tissue types to focus on such relationships in 94 genes linked to hypermethylated DMRs in myoblasts (Mb). For 19 of the genes, promoter-region hypermethylation in Mb (and often a few heterologous cell types) was associated with gene repression but, importantly, DNA hypermethylation was absent in many other repressed samples...
March 2, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Xiao Dong, Miao Shi, Moonsook Lee, Rafael Toro, Silvia Gravina, Weiguo Han, Shoya Yasuda, Tao Wang, Zhengdong Zhang, Jan Vijg, Yousin Suh, Simon D Spivack
Gene regulatory analysis of highly diverse human tissues in vivo is essentially constrained by the challenge of performing genome-wide, integrated epigenetic and transcriptomic analysis in small selected groups of specific cell types. Here we performed genome-wide bisulfite sequencing and RNA-seq from the same small groups of bronchial and alveolar cells isolated by laser capture microdissection from flash-frozen lung tissue of 12 donors and their peripheral blood T cells. Methylation and transcriptome patterns differed between alveolar and bronchial cells, while each of these epithelia showed more differences from mesodermally-derived T cells...
February 21, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Hui-Chen Wu, Catherine Do, Irene L Andrulis, Esther M John, Mary B Daly, Saundra S Buys, Wendy K Chung, Julia A Knight, Angela R Bradbury, Theresa H M Keegan, Lisa Schwartz, Izabela Krupska, Rachel L Miller, Regina M Santella, Benjamin Tycko, Mary Beth Terry
Family history, a well-established risk factor for breast cancer, can have both genetic and environmental contributions. Shared environment in families as well as epigenetic changes that also may be influenced by shared genetics and environment may also explain familial clustering of cancers. Epigenetic regulation, such as DNA methylation, can change the activity of a DNA segment without a change in the sequence; environmental exposures experienced across the life course can induce such changes. However, genetic-epigenetic interactions, detected as methylation quantitative trait loci (mQTLs; a...
February 13, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Olga Vera, Carlos Rodriguez-Antolin, Javier de Castro, Florian A Karreth, Thomas A Sellers, Inmaculada Ibañez de Caceres
Long noncoding RNAs (lncRNAs) are critical regulators of cell biology whose alteration can lead to the development of diseases such as cancer. The potential role of lncRNAs and their epigenetic regulation in response to platinum treatment are largely unknown. We analyzed four paired cisplatin-sensitive/resistant non-small cell lung cancer and ovarian cancer cell lines. The epigenetic landscape of overlapping and cis-acting lncRNAs was determined by combining human microarray data on 30,586 lncRNAs and 20,109 protein coding mRNAs with whole-genome bisulfite sequencing...
February 13, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Albert Jordan, Albert Carbonell, Raquel Fueyo, Andrea Izquierdo-Bouldstridge, Cristina Moreta
The Barcelona Conference on Epigenetics and Cancer (BCEC) entitled "Epigenetic Mechanisms in Health and Disease" was held in Barcelona, October 26-26, 2017. The 2017 BCEC was the fifth and last edition of a series of annual conferences organized as a joint effort of five leading Barcelona research institutes together with B-Debate. This edition was organized by Albert Jordan from the Molecular Biology Institute of Barcelona (IBMB-CSIC) and Marcus Bushbeck from the Josep Carreras Leukaemia Research Institute (IJC)...
January 31, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Marie Forest, Kieran J O'Donnell, Greg Voisin, Helene Gaudreau, Julia L MacIsaac, Lisa M McEwen, Patricia P Silveira, Meir Steiner, Michael S Kobor, Michael J Meaney, Celia M T Greenwood
Epigenome-wide association studies (EWAS) have focused primarily on DNA methylation as a chemically stable and functional epigenetic modification. However, the stability and accuracy of the measurement of methylation in different tissues and extraction types is still being actively studied, and the longitudinal stability of DNA methylation in commonly studied peripheral tissues is of great interest. Here, we used data from two studies, three tissue types, and multiple time points to assess the stability of DNA methylation measured with the Illumina Infinium HumanMethylation450 BeadChip array...
January 30, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Sungsam Gong, Michelle D Johnson, Justyna Dopierala, Francesca Gaccioli, Ulla Sovio, Miguel Constância, Gordon Cs Smith, D Stephen Charnock-Jones
DNA methylation is an important regulator of gene function. Fetal sex is associated with the risk of several specific pregnancy complications related to placental function. However, the association between fetal sex and placental DNA methylation remains poorly understood. We carried out whole-genome oxidative bisulfite sequencing in the placentas of two healthy female and two healthy male pregnancies generating an average genome depth of coverage of 25x. Most highly ranked differentially methylated regions (DMRs) were located on the X chromosome but we identified a 225 kb sex-specific DMR in the body of the CUB and Sushi Multiple Domains 1 (CSMD1) gene on chromosome 8...
January 29, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Mathia Colwell, Melissa Drown, Kelly Showel, Chelsea Drown, Amanda Palowski, Christopher Faulk
Ultraconserved noncoding elements (UCNEs) constitute less than 1 Mb of vertebrate genomes and are impervious to accumulating mutations. About 4000 UCNEs exist in vertebrate genomes, each at least 200 nucleotides in length, sharing greater than 95% sequence identity between human and chicken. Despite extreme sequence conservation over 400 million years of vertebrate evolution, we show both ordered interspecies and within-species interindividual variation in DNA methylation in these regions. Here, we surveyed UCNEs with high CpG density in 56 species finding half to be intermediately methylated and the remaining near 0% or 100%...
January 26, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Tristan Henser-Brownhill, Josep Monserrat, Paola Scaffidi
The CRISPR-Cas9 system has revolutionized genome engineering, allowing precise modification of DNA in various organisms. The most popular method for conducting CRISPR-based functional screens involves the use of pooled lentiviral libraries in selection screens coupled with next-generation sequencing. Screens employing genome-scale pooled small guide RNA (sgRNA) libraries are demanding, particularly when complex assays are used. Furthermore, pooled libraries are not suitable for microscopy-based high-content screens or for systematic interrogation of protein function...
January 12, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Eugene Nyamugenda, A Brandon Cox, Jacob B Pierce, Ryan C Banning, Michelle L Huynh, Catey May, Sarah Marshall, Claire E Turkal, Andrea A Duina
Previous work in Saccharomyces cerevisiae identified three residues located in close proximity to each other on the side of the nucleosome whose integrity is required for proper association of the Spt16 component of the FACT complex across transcribed genes. In an effort to gain further insights into the parameters that control Spt16 interactions with genes in vivo, we tested the effects of additional histone mutants on Spt16 occupancy across two constitutively transcribed genes. These studies revealed that mutations in several charged residues in the vicinity of the three residues originally identified as important for Spt16-gene interactions also significantly perturb normal association of Spt16 across genes...
December 22, 2017: Epigenetics: Official Journal of the DNA Methylation Society
John Dou, Rebecca J Schmidt, Kelly S Benke, Craig Newschaffer, Irva Hertz-Picciotto, Lisa A Croen, Ana-Maria Iosif, Janine M LaSalle, M Daniele Fallin, Kelly M Bakulski
Cord blood DNA methylation is associated with numerous health outcomes and environmental exposures. Whole cord blood DNA reflects all nucleated blood cell types, while centrifuging whole blood separates red blood cells, generating a white blood cell buffy coat. Both sample types are used in DNA methylation studies. Cell types have unique methylation patterns and processing can impact cell distributions, which may influence comparability. We evaluated differences in cell composition and DNA methylation between cord blood buffy coat and whole cord blood samples...
2018: Epigenetics: Official Journal of the DNA Methylation Society
Katerina Rejlova, Alena Musilova, Karolina Skvarova Kramarzova, Marketa Zaliova, Karel Fiser, Meritxell Alberich-Jorda, Jan Trka, Julia Starkova
Homeobox (HOX) genes are frequently dysregulated in leukemia. Previous studies have shown that aberrant HOX gene expression accompanies leukemogenesis and affects disease progression and leukemia patient survival. Patients with acute myeloid leukemia (AML) bearing PML-RARα fusion gene have distinct HOX gene signature in comparison to other subtypes of AML patients, although the mechanism of transcription regulation is not completely understood. We previously found an association between the mRNA levels of HOX genes and those of the histone demethylases JMJD3 and UTX in PML-RARα- positive leukemia patients...
2018: Epigenetics: Official Journal of the DNA Methylation Society
Lukas Vrba, Bernard W Futscher
Cancer-specific DNA methylation from the tumor derived fraction of cell free DNA found in blood samples could be used for minimally invasive detection and monitoring of cancer. The knowledge of marker regions with cancer-specific DNA methylation is necessary to the success of such a process. We analyzed the largest cancer DNA methylation dataset available-TCGA Illumina HumanMethylation450 data with over 8,500 tumors-in order to find cancer-specific DNA methylation markers for most common human cancers. First, we identified differentially methylated regions for individual cancer types and those were further filtered against data from normal tissues to obtain marker regions with cancer-specific methylation, resulting in a total of 1,250 hypermethylated and 584 hypomethylated marker CpGs...
2018: Epigenetics: Official Journal of the DNA Methylation Society
Anna K Knight, Karen N Conneely, Varun Kilaru, Dawayland Cobb, Jennifer L Payne, Samantha Meilman, Elizabeth J Corwin, Zachary A Kaminsky, Anne L Dunlop, Alicia K Smith
Fetal intolerance of labor is a common indication for delivery by Caesarean section. Diagnosis is based on the presence of category III fetal heart rate tracing, which is an abnormal heart tracing associated with increased likelihood of fetal hypoxia and metabolic acidemia. This study analyzed data from 177 unique women who, during their prenatal visits (7-15 weeks and/or 24-32 weeks) to Atlanta area prenatal care clinics, consented to provide blood samples for DNA methylation (HumanMethylation450 BeadChip) and gene expression (Human HT-12 v4 Expression BeadChip) analyses...
December 13, 2017: Epigenetics: Official Journal of the DNA Methylation Society
Alexandra M Binder, Camila Corvalan, Verónica Mericq, Ana Pereira, José Luis Santos, Steve Horvath, John Shepherd, Karin B Michels
Epigenetic age is an indicator of biological aging, capturing the impact of environmental and behavioral influences across time on cellular function. Deviance between epigenetic age and chronological age (AgeAccel) is a predictor of health. Pubertal timing has similarly been associated with cancer risk and mortality rate among females. We examined the association between AgeAccel and pubertal timing and adolescent breast composition in the longitudinal Growth and Obesity Cohort Study. AgeAccel was estimated in whole blood using the Horvath method at breast Tanner 2 (B2) and 4 (B4)...
December 13, 2017: Epigenetics: Official Journal of the DNA Methylation Society
Catherine E Bond, Cheng Liu, Futoshi Kawamata, Diane M McKeone, Winnie Fernando, Saara Jamieson, Sally-Ann Pearson, Alexandra Kane, Susan L Woods, Tamsin R M Lannagan, Roshini Somashekar, Young Lee, Troy Dumenil, Gunter Hartel, Kevin J Spring, Jennifer Borowsky, Lochlan Fennell, Mark Bettington, Jason Lee, Daniel L Worthley, Barbara A Leggett, Vicki L J Whitehall
Colorectal cancer is a major cause of cancer death and approximately 20% arises within serrated polyps, which are under-recognized and poorly understood. Human serrated colorectal polyps frequently exhibit both oncogenic BRAF mutation and widespread DNA methylation changes, which are important in silencing genes restraining neoplastic progression. Here, we investigated whether in vivo induction of mutant Braf is sufficient to result in coordinated promoter methylation changes for multiple cancer-related genes...
December 13, 2017: Epigenetics: Official Journal of the DNA Methylation Society
Teresa Morales-Ruiz, María Victoria García-Ortiz, Iván Devesa-Guerra, Laura Raya-Ruiz, Juan R Tejedor, Gustavo F Bayón, Marta I Sierra, Mario F Fraga, Rafael R Ariza, Teresa Roldán-Arjona
Patterns of DNA methylation, an important epigenetic modification involved in gene silencing and development, are disrupted in cancer cells. Understanding the functional significance of aberrant methylation in tumors remains challenging, due in part to the lack of suitable tools to actively modify methylation patterns. DNA demethylation caused by mammalian DNA methyltransferase inhibitors is transient and replication-dependent, whereas that induced by TET enzymes involves oxidized 5mC derivatives that perform poorly understood regulatory functions...
December 13, 2017: Epigenetics: Official Journal of the DNA Methylation Society
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