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Epigenetics: Official Journal of the DNA Methylation Society

L Fontana, M F Bedeschi, S Maitz, A Cereda, C Faré, S Motta, A Seresini, P D'Ursi, A Orro, V Pecile, M Calvello, A Selicorni, F Lalatta, D Milani, S M Sirchia, M Miozzo, S Tabano
The identification of multi-locus imprinting disturbances (MLID) appears fundamental to uncover molecular pathways underlying imprinting disorders (IDs) and to complete clinical diagnosis of patients. However, MLID genetic associated mechanisms remain largely unknown. To characterize MLID in Beckwith-Wiedemann (BWS) and Silver-Russell (SRS) syndromes, we profiled by MassARRAY the methylation of 12 imprinted differentially methylated regions (iDMRs) in 21 BWS and 7 SRS patients with chromosome 11p15.5 epimutations...
September 16, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Eric Nilsson, Rachel Klukovich, Ingrid Sadler-Riggleman, Daniel Beck, Yeming Xie, Wei Yan, Michael K Skinner
Two of the most prevalent ovarian diseases affecting women's fertility and health are Primary Ovarian Insufficiency (POI) and Polycystic Ovarian Syndrome (PCOS). Previous studies have shown that exposure to a number of environmental toxicants can promote the epigenetic transgenerational inheritance of ovarian disease. In the current study, transgenerational changes to the transcriptome and epigenome of ovarian granulosa cells are characterized in F3 generation rats after ancestral vinclozolin or DDT exposures...
September 12, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Anne Bozack, Andres Cardenas, Quazi Quamruzzaman, Mahmuder Rahman, Golam Mostofa, David C Christiani, Molly L Kile
Prenatal arsenic exposure is associated with adverse birth outcomes and disease risk later in life, which could be mediated through epigenetic dysregulation. We evaluated the association between arsenic and gestational age (GA) that was mediated through DNA methylation (DNAm) using data from a Bangladeshi birth cohort. Arsenic exposure was measured in maternal drinking water at ≤16 weeks GA and maternal toenails collected <1 month postpartum. Cord blood DNAm was measured using Infinium HumanMethylation450 arrays (n=44, discovery phase)...
September 3, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Aziz Khan, Anthony Mathelier, Xuegong Zhang
Super-enhancers and stretch enhancers represent classes of transcriptional enhancers that have been shown to control the expression of cell identity genes and carry disease- and trait-associated variants. Specifically, super-enhancers are clusters of enhancers defined based on the binding occupancy of master transcription factors, chromatin regulators, or chromatin marks, while stretch enhancers are large chromatin-defined regulatory regions of at least 3,000 base pairs. Several studies have characterized these regulatory regions in numerous cell types and tissues to decipher their functional importance...
August 31, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Oriana Lo Re, Julien Douet, Marcus Buschbeck, Caterina Fusilli, Valerio Pazienza, Concetta Panebianco, Carlo Castruccio Castracani, Tommaso Mazza, Giovanni Li Volti, Manlio Vinciguerra
Hepatocellular carcinomas (HCCs) contain a sub-population of cancer stem cells (CSCs) that are responsible for tumor relapse, metastasis, and chemoresistance. We recently showed that loss of macroH2A1, a variant of the histone H2A and an epigenetic regulator of stem-cell function, in HCC leads to CSC-like features such as resistance to chemotherapeutic agents and growth of large and relatively undifferentiated tumors in xenograft models. These HCC cells silenced for macroH2A1 also exhibited stem-like metabolic changes consistent with enhanced glycolysis...
August 30, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Xu Gao, Yan Zhang, Ute Mons, Hermann Brenner
Telomere length (TL) has been established as a biomarker of aging and aging-related health outcomes, but showed only a weak or inconsistent association with all-cause mortality in previous epidemiological studies. Recently, an epigenetic "mortality risk score" (MS) based on whole blood DNA methylation at 10 mortality-related CpG sites has been demonstrated to be strongly related to all-cause mortality at the population level. This study aimed to address the association between TL and this MS, and to assess and compare their associations with all-cause mortality...
August 28, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Olutobi Oyinlade, Shuang Wei, Kai Kammers, Sheng Liu, Shuyan Wang, Ding Ma, Zhi-Yong Huang, Jiang Qian, Heng Zhu, Jun Wan, Shuli Xia
Recent studies have revealed an unexpected role of DNA methylation at promoter regions in transcription activation. However, whether DNA methylation at enhancer regions activates gene expression and influences cellular functions remains to be determined. In this study, by employing the transcription factor krÜppel-like factor 4 (KLF4) that binds to methylated CpGs (mCpGs), we investigated the molecular outcomes of the recruitment of KLF4 to mCpGs at enhancer regions in human glioblastoma cells. First, by integrating KLF4 ChIP-seq, whole-genome bisulfite sequence, and H3K27ac ChIP-seq datasets, we found 1,299 highly methylated (β >0...
August 25, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Fushun Chen, Qingzheng Zhang, Xiaodi Deng, Xia Zhang, Chengjun Chen, Dekang Lv, Yulong Li, Dan Li, Yu Zhang, Peiying Li, Yunpeng Diao, Lan Kang, Gareth I Owen, Jun Chen, Zhiguang Li
The relationship between CpG content and DNA methylation has attracted considerable interest in recent years. Direct or indirect methods have been developed to investigate their regulatory functions based on various hypotheses, large cohort studies, and meta-analyses. However, all of these analyses were performed at units of CpG blocks and, thus, the influence of finer genome structure has been neglected. Herein, we present a novel algorithm of base-pair resolution to systematically investigate the relationship between CpG contents and DNA methylation...
August 25, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Wina Verlaat, Robert W Van Leeuwen, Putri W Novianti, Ed Schuuring, Chris J L M Meijer, Ate G J Van Der Zee, Peter J F Snijders, Daniëlle A M Heideman, Renske D M Steenbergen, G Bea A Wisman
Cervical cancer development following a persistent infection with high-risk human papillomavirus (hrHPV) is driven by additional host-cell changes, such as altered DNA methylation. In previous studies, we have identified 12 methylated host genes associated with cervical cancer and pre-cancer (CIN2/3). This study systematically analyzed the onset and DNA methylation pattern of these genes during hrHPV-induced carcinogenesis using a longitudinal in vitro model of hrHPV-transformed cell lines (n = 14) and hrHPV-positive cervical scrapings (n = 113) covering various stages of cervical carcinogenesis...
August 24, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Michiko Hirose, Masashi Hada, Satoshi Kamimura, Shogo Matoba, Arata Honda, Kaori Motomura, Narumi Ogonuki, Hossam H Shawki, Kimiko Inoue, Satoru Takahashi, Atsuo Ogura
Although phenotypic abnormalities frequently appear in the placenta following somatic cell nuclear transfer (SCNT), mouse trophoblast stem cells (TSCs) established from SCNT embryos reportedly show no distinct abnormalities compared with those derived from normal fertilization. In this study, we reexamined SCNT-TSCs to identify their imprinting statuses. Placenta-specific maternally imprinted genes (Gab1, Slc38a4, and Sfmbt2) consistently showed biallelic expression in SCNT-TSCs, suggesting their loss of imprinting (LOI)...
August 23, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Joseph Kochmanski, Elizabeth H Marchlewicz, Raymond G Cavalcante, Maureen A Sartor, Dana C Dolinoy
DNA methylation at cytosine-phosphate-guanine (CpG) dinucleotides changes as a function of age in humans and animal models, a process that may contribute to chronic disease development. Recent studies have investigated the role of an oxidized form of DNA methylation - 5-hydroxymethylcytosine (5hmC) - in the epigenome, but its contribution to age-related DNA methylation remains unclear. We tested the hypothesis that 5hmC changes with age, but in a direction opposite to 5-methylcytosine (5mC), potentially playing a distinct role in aging...
August 23, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Brianna J Klein, Krzysztof Krajewski, Susana Restrepo, Peter W Lewis, Brian D Strahl, Tatiana G Kutateladze
Histone posttranslational modifications control the organization and function of chromatin. In particular, methylation of lysine 36 in histone H3 (H3K36me) has been shown to mediate gene transcription, DNA repair, cell cycle regulation, and pre-mRNA splicing. Notably, mutations at or near this residue have been causally linked to the development of several human cancers. These observations have helped to illuminate the role of histones themselves in disease and to clarify the mechanisms by which they acquire oncogenic properties...
August 23, 2018: 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...
August 15, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Heather H Burris, Allan C Just, Miriam J Haviland, Dayna T Neo, Andrea A Baccarelli, Alexandra E Dereix, Kasey J Brennan, Rodosthenis S Rodosthenous, Steven J Ralston, Jonathan L Hecht, Michele R Hacker
Infants born preterm are at increased risk of multiple morbidities and mortality. Why some women deliver preterm remains poorly understood. Prior studies have shown that cervical microRNA expression and DNA methylation are associated with the length of gestation. However, no study has examined the role of long noncoding RNAs (lncRNAs) in the cervix during pregnancy. To determine whether expression of lncRNAs is associated with length of gestation at delivery, we analyzed RNA from cervical swabs obtained from 78 women during pregnancy (mean 15...
August 10, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Jingyue Ellie Duan, Mingyuan Zhang, Kaleigh Flock, Sahar Al Seesi, Ion Mandoiu, Amanda Jones, Elizabeth Johnson, Sambhu Pillai, Maria Hoffman, Katelyn McFadden, Hesheng Jiang, Sarah Reed, Kristen Govoni, Steve Zinn, Zongliang Jiang, Xiuchun Cindy Tian
Genomic imprinting is an epigenetic phenomenon of differential allelic expression based on parental origin. To date, 263 imprinted genes have been identified among all investigated mammalian species. However, only 21 have been described in sheep, of which 11 are annotated in the current ovine genome. Here, we aim to i) use DNA/RNA high throughput sequencing to identify new monoallelically expressed and imprinted genes in day 135 ovine fetuses, and ii) determine whether maternal diet (100%, 60%, or 140% of National Research Council Total Digestible Nutrients) influences expression of imprinted genes...
July 27, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Mohammad L Rahman, Liming Liang, Linda Valeri, Li Su, Zhaozhong Zhu, Shangzhi Gao, Golam Mostofa, Qazi Qamruzzaman, Russ Hauser, Andrea Baccarelli, David C Christiani
Altered expression of microRNAs (miRNAs) is implicated in fetal growth. However, the mechanisms by which placenta-derived miRNAs regulate birthweight are not well understood. In Phase 1, we compared the expression of 754 miRNAs in the placenta of mothers from two extreme birthweight groups (0.8-2.2 kg vs. 3.3-3.9 kg, n = 77 each) selected from an arsenic-exposed Bangladeshi birth cohort (n = 1,141). We identified 49 miRNAs associated with the extreme birthweight groups and/or gestational age in Phase 1, which were further analyzed in Phase 2 among 364 randomly selected mother-infant pairs...
2018: Epigenetics: Official Journal of the DNA Methylation Society
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...
2018: Epigenetics: Official Journal of the DNA Methylation Society
Lusy Handoko, Bogumil Kaczkowski, Chung-Chau Hon, Marina Lizio, Masatoshi Wakamori, Takayoshi Matsuda, Takuhiro Ito, Prashanti Jeyamohan, Yuko Sato, Kensaku Sakamoto, Shigeyuki Yokoyama, Hiroshi Kimura, Aki Minoda, Takashi Umehara
The bromodomain and extra-terminal domain (BET) proteins are promising drug targets for cancer and immune diseases. However, BET inhibition effects have been studied more in the context of bromodomain-containing protein 4 (BRD4) than BRD2, and the BET protein association to histone H4-hyperacetylated chromatin is not understood at the genome-wide level. Here, we report transcription start site (TSS)-resolution integrative analyses of ChIP-seq and transcriptome profiles in human non-small cell lung cancer (NSCLC) cell line H23...
2018: Epigenetics: Official Journal of the DNA Methylation Society
David L Marks, Rachel L Olson, Raul Urrutia, Daniel D Billadeau, Nilotpal Roy, George A Calin, Muller Fabbri, Marina Koutsioumpa, Dimitrios Iliopoulos, Tamas Ordog, Robert Huebert, Olga Sarmento, Adebowale O Bamidele, William Faubion, Gwen L Lomberk, Jens Siveke, Nita Ahuja, Juan Iovanna, Ryan A Hlady, Keith Robertson, John Kisiel, Christopher L Pin, Martin E Fernandez-Zapico
International experts gathered at the Mayo Clinic (Rochester MN, USA) on February 27th-28th, 2017 for a meeting entitled 'Basic and Translational Facets of the Epigenetics of GI Diseases'. This workshop summarized recent advances on the role of epigenetics in the pathobiology of gastrointestinal (GI) diseases. Highlights of the meeting included recent advances on the involvement of different epigenetic mechanisms in malignant and nonmalignant GI disorders and the epigenetic heterogeneity exhibited in these diseases...
2018: Epigenetics: Official Journal of the DNA Methylation Society
Olivia Solomon, Julie MacIsaac, Hong Quach, Gwen Tindula, Michael S Kobor, Karen Huen, Michael J Meaney, Brenda Eskenazi, Lisa F Barcellos, Nina Holland
Analysis of DNA methylation helps to understand the effects of environmental exposures as well as the role of epigenetics in human health. Illumina, Inc. recently replaced the HumanMethylation450 BeadChip (450K) with the EPIC BeadChip, which nearly doubles the measured CpG sites to >850,000. Although the new chip uses the same underlying technology, it is important to establish if data between the two platforms are comparable within cohorts and for meta-analyses. DNA methylation was assessed by 450K and EPIC using whole blood from newborn (n = 109) and 14-year-old (n = 86) participants of the Center for the Health Assessment of Mothers and Children of Salinas...
2018: Epigenetics: Official Journal of the DNA Methylation Society
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