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Epigenetics: Official Journal of the DNA Methylation Society

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https://www.readbyqxmd.com/read/28886276/systems-approach-to-the-pharmacological-actions-of-hdac-inhibitors-reveals-ep300-activities-and-convergent-mechanisms-of-regulation-in-diabetes
#1
Haloom Rafehi, Antony Kaspi, Mark Ziemann, Jun Okabe, Tom C Karagiannis, Assam El-Osta
Given the skyrocketing costs to develop new drugs, repositioning of approved drugs, such as histone deacetylase (HDAC) inhibitors, may be a promising strategy to develop novel therapies. However, a gap exists in the understanding and advancement of these agents to meaningful translation for which new indications may emerge. To address this, we performed systems-level analyses of 33 independent HDAC inhibitor microarray studies. Based on network analysis, we identified enrichment for pathways implicated in metabolic syndrome and diabetes (insulin receptor signaling, lipid metabolism, immunity and trafficking)...
September 8, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28837395/nightshift-work-chronotype-and-genome-wide-dna-methylation-in-blood
#2
Charleen D Adams, Kristina M Jordahl, Wade Copeland, Dana K Mirick, Xiaoling Song, Cassandra L Sather, Karl Kelsey, Andres Houseman, Scott Davis, Timothy Randolph, Parveen Bhatti
Molecular mechanisms underlying the negative health effects of shift work are poorly understood, which remains a barrier to developing intervention strategies to protect the long-term health of shift workers. We evaluated genome-wide differences in DNA methylation (measured in blood) between 111 actively employed female nightshift and 86 actively employed female dayshift workers from the Seattle metropolitan area. We also explored the effect of chronotype (i.e., measure of preference for activity earlier or later in the day) on DNA methylation among 110 of the female nightshift workers and an additional group of 131 male nightshift workers...
August 24, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28820654/locus-specific-dna-methylation-in-the-placenta-is-associated-with-levels-of-pro-inflammatory-proteins-in-cord-blood-and-they-are-both-independently-affected-by-maternal-smoking-during-pregnancy
#3
Sanne D van Otterdijk, Alexandra M Binder, Karin B Michels
We investigated the impact of maternal smoking during pregnancy on placental DNA methylation and how this may mediate the association between maternal smoking and pro-inflammatory proteins in cord blood. The study population consisted of 27 individuals exposed to maternal smoking throughout pregnancy, 32 individuals exposed during a proportion of the pregnancy, and 61 unexposed individuals. Methylation of 11 regions within 6 genes in placenta tissue was assessed by pyrosequencing. Levels of 7 pro-inflammatory proteins in cord blood were assessed by electrochemiluminescence...
August 18, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28816587/dna-methylation-independent-growth-restriction-and-altered-developmental-programming-in-a-mouse-model-of-preconception-male-alcohol-exposure
#4
Richard C Chang, William M Skiles, S Chronister Sarah, Haiqing Wang, Gabrielle I Sutton, Yudhishtar S Bedi, Matthew Snyder, Charles R Long, Michael C Golding
The preconception environment is a significant modifier of dysgenesis and the development of environmentally-induced disease. To date, Fetal Alcohol Spectrum Disorders (FASDs) have been exclusively associated with maternal exposures, yet emerging evidence suggests male-inherited alterations in the developmental program of sperm may be relevant to the growth-restriction phenotypes of this condition. Using a mouse model of voluntary consumption, we find chronic preconception male ethanol exposure associates with fetal growth restriction, decreased placental efficiency, abnormalities in cholesterol trafficking, sex-specific alterations in the genetic pathways regulating hepatic fibrosis, and disruptions in the regulation of imprinted genes...
August 17, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28762874/reactivation-of-hyperglycemia-induced-hypocretin-hcrt-gene-silencing-by-n-acetyl-d-mannosamine-in-the-orexin-neurons-derived-from-human-ips-cells
#5
Koji Hayakawa, Yasuharu Sakamoto, Osamu Kanie, Atsuko Ohtake, Shusaku Daikoku, Yukishige Ito, Kunio Shiota
Orexin neurons regulate critical brain activities for controlling sleep, eating, emotions, and metabolism, and impaired orexin neuron function results in several neurological disorders. Therefore, restoring normal orexin function and understanding the mechanisms of loss or impairment of orexin neurons represent important goals. As a step toward that end, we generated human orexin neurons from induced pluripotent stem cells (hiPSCs) by treatment with N-acetyl-d-mannosamine (ManNAc) and its derivatives. The generation of orexin neurons was associated with DNA hypomethylation, histone H3/H4 hyperacetylation, and hypo-O-GlcNAcylation on the HCRT gene locus, and, thereby, the treatment of inhibitors of SIRT1 and OGT were effective at inducing orexin neurons from hiPSCs...
August 1, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28758855/targeting-dna-hypermethylation-computational-modeling-of-dna-demethylation-treatment-of-acute-myeloid-leukemia
#6
Jens Przybilla, Lydia Hopp, Michael Lübbert, Markus Loeffler, Joerg Galle
In acute myeloid leukemia (AML) DNA hypermethylation of gene promoters is frequently observed and often correlates with a block of differentiation. Treatment of AML patients with DNA methyltransferase inhibitors results in global hypomethylation of genes and, thereby, can lead to a reactivation of the differentiation capability. Unfortunately, after termination of treatment both hypermethylation and differentiation block return in most cases. Here, we apply, for the first time, a computational model of epigenetic regulation of transcription in order to: i) provide a mechanistic understanding of the DNA (de-) methylation process in AML and; ii) improve DNA demethylation treatment strategies...
July 31, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28758831/tet1-deficiency-attenuates-the-dna-damage-response-and-promotes-resistance-to-dna-damaging-agents
#7
Jonathan B Coulter, Hernando Lopez-Bertoni, Katherine J Kuhns, Richard S Lee, John Laterra, Joseph P Bressler
Recent studies have shown that loss of TET1 may play a significant role in the formation of tumors. Because genomic instability is a hallmark of cancer, we examined the potential involvement of ten-eleven translocation 1 (TET1) in the DNA damage response (DDR). Here we demonstrate that, in response to clinically relevant doses of ionizing radiation (IR), human glial cells made TET1-deficient with lentiviral vectors displayed greater numbers of colony forming units and lower levels of apoptotic markers compared to glial cells transduced with control vectors; yet, they harbored greater DNA strand breaks...
July 31, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28758828/second-trimester-extracellular-micrornas-in-maternal-blood-and-fetal-growth-an-exploratory-study
#8
Rodosthenis S Rodosthenous, Heather H Burris, Alison P Sanders, Allan C Just, Alexandra E Dereix, Katherine Svensson, Maritsa Solano, Martha M Téllez-Rojo, Robert O Wright, Andrea A Baccarelli
Healthy feto-maternal communication is critical during pregnancy and is orchestrated by the placenta. Dysfunction of the placenta leads to fetal growth complications; however, the underlying biological mechanisms have yet to be fully elucidated. Circulating extracellular microRNAs (exmiRNAs) in the blood have been implicated in cell-to-cell communication. Therefore, exmiRNAs may provide useful biological information about communication between the mother, the fetus, and the placenta during pregnancy. We used logistic regression to determine the association of exmiRNAs with abnormal fetal growth by comparing mothers of infants classified as small-for-gestational age (SGA) (n = 36) and large-for-gestational age (LGA) (n = 13) to appropriate-for-gestational age (AGA), matched by gestational age at delivery and infant sex...
July 31, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28753106/colorectal-adenoma-and-cancer-detection-based-on-altered-methylation-pattern-of-sfrp1-sfrp2-sdc2-and-prima1-in-plasma-samples
#9
Barbara Kinga Barták, Alexandra Kalmár, Bálint Péterfia, Árpád V Patai, Orsolya Galamb, Gábor Valcz, Sándor Spisák, Barnabás Wichmann, Zsófia Brigitta Nagy, Kinga Tóth, Zsolt Tulassay, Péter Igaz, Béla Molnár
Aberrant methylation is one of the most frequent epigenetic alterations that can contribute to tumor formation. Cell-free DNA can originate from tumor tissue; therefore, the evaluation of methylation markers in cell-free DNA can be a promising method for cancer screening. Our aim was to develop a panel of biomarkers with altered methylation along colorectal adenoma-carcinoma sequence in both colonic tissue and plasma. The methylation of selected CpG sites in healthy colonic (n = 15), adenoma (n = 15), and colorectal cancer (n = 15) tissues was analyzed by pyrosequencing...
July 28, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28749240/epigenetic-dysregulation-of-the-erythropoietic-transcription-factor-klf1-and-the-%C3%AE-like-globin-locus-in-juvenile-myelomonocytic-leukemia
#10
Silvia Fluhr, Christopher Felix Krombholz, Angelina Meier, Thomas Epting, Oliver Mücke, Christoph Plass, Charlotte M Niemeyer, Christian Flotho
Increased levels of fetal hemoglobin (HbF) are a hallmark of more than half of the children diagnosed with juvenile myelomonocytic leukemia (JMML). Elevated HbF levels in JMML are associated with DNA hypermethylation of distinct gene promoter regions in leukemic cells. Since the regulation of globin gene transcription is known to be under epigenetic control, we set out to study the relation of DNA methylation patterns at β-/γ-globin promoters, mRNA and protein expression of globins, and epigenetic modifications of genes encoding the globin-regulatory transcription factors BCL11A and KLF1 in nucleated erythropoietic precursor cells of patients with JMML...
July 27, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28742980/disease-relevant-modifications-of-the-methylome-and-transcriptome-by-particulate-matter-pm2-5-from-biomass-combustion
#11
Katharina Heßelbach, Gwang-Jin Kim, Stephan Flemming, Thomas Häupl, Marc Bonin, Regina Dornhof, Stefan Günther, Irmgard Merfort, Matjaz Humar
Exposure to particulate matter (PM) is recognized as a major health hazard, but molecular responses are still insufficiently described. We analyzed the epigenetic impact of ambient PM2.5 from biomass combustion on the methylome of primary human bronchial epithelial BEAS-2B cells using the Illumina HumanMethylation450 BeadChip. The transcriptome was determined by the Affymetrix HG-U133 Plus 2.0 Array. PM2.5 induced genome wide alterations of the DNA methylation pattern, including differentially methylated CpGs in the promoter region associated with CpG islands...
July 25, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28703682/a-mbd-seq-protocol-for-large-scale-methylome-wide-studies-with-very-low-amounts-of-dna
#12
Karolina A Aberg, Robin F Chan, Andrey A Shabalin, Min Zhao, Gustavo Turecki, Nicklas Heine Staunstrup, Anna Starnawska, Ole Mors, Lin Y Xie, Edwin J C G van den Oord
We recently showed that, after optimization, our methyl-CpG binding domain sequencing (MBD-seq) application approximates the methylome-wide coverage obtained with whole-genome bisulfite sequencing (WGB-seq), but at a cost that enables adequately powered large-scale association studies. A prior drawback of MBD-seq is the relatively large amount of genomic DNA (ideally >1 μg) required to obtain high-quality data. Biomaterials are typically expensive to collect, provide a finite amount of DNA, and may simply not yield sufficient starting material...
July 13, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28703658/epigenetic-silencing-of-mir-203-in-kazakh-patients-with-esophageal-squamous-cell-carcinoma-by-massarray-spectrometry
#13
Xiaobin Cui, Xi Chen, Weiwei Wang, Aimin Chang, Lan Yang, Chunxia Liu, Hao Peng, Yutao Wei, Weihua Liang, Shugang Li, Ning Wang, Wei Liu, Jianming Hu, Wenjie Zhang, Lidong Wang, Yunzhao Chen, Feng Li
Dysregulation of miR-203 by promoter methylation is associated with the development of various cancers. We aimed to explore the underlying link between promoter methylation and miR-203 expression in Kazakh esophageal squamous cell carcinoma (ESCC). MassARRAY® System spectrometry was used to quantitatively analyze the DNA methylation of 32 CpG sites within miR-203 in 99 Kazakh ESCC and 46 normal esophageal tissues (NETs) with similar population characteristics. We conducted real-time PCR to detect miR-203 expression levels and evaluated their association with methylation...
July 13, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28678681/profiling-of-oxbs-450k-5-hydroxymethylcytosine-in-human-placenta-and-brain-reveals-enrichment-at-imprinted-loci
#14
Jose Ramon Hernandez Mora, Marta Sanchez-Delgado, Paolo Petazzi, Sebastian Moran, Manel Esteller, Isabel Iglesias-Platas, David Monk
DNA methylation (5-methylcytosine, 5mC) is involved in many cellular processes and is an epigenetic mechanism primarily associated with transcriptional repression. The recent discovery that 5mC can be oxidized to 5-hydromethylcytosine (5hmC) by TET proteins has revealed the "sixth base" of DNA and provides additional complexity to what was originally thought to be a stable repressive mark. However, our knowledge of the genome-wide distribution of 5hmC in different tissues is currently limited. Here, we sought to define loci enriched for 5hmC in the placenta genome by combining oxidative bisulphite (oxBS) treatment with high-density Illumina Infinium HumanMethylation450 methylation arrays and to compare our results with those obtained in brain...
July 5, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28678605/the-early-pregnancy-placenta-foreshadows-dna-methylation-alterations-of-solid-tumors
#15
Akpéli V Nordor, Djamel Nehar-Belaid, Sophie Richon, David Klatzmann, Dominique Bellet, Virginie Dangles-Marie, Thierry Fournier, Martin J Aryee
The placenta relies on phenotypes that are characteristic of cancer to successfully implant the embryo in the uterus during early pregnancy. Notably, it has to invade its host tissues, promote angiogenesis-while surviving hypoxia-, and escape the immune system. Similarities in DNA methylation patterns between the placenta and cancers suggest that common epigenetic mechanisms may be involved in regulating these behaviors. We show here that megabase-scale patterns of hypomethylation distinguish first from third trimester chorionic villi in the placenta, and that these patterns mirror those that distinguish many tumors from corresponding normal tissues...
July 5, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28678596/maternal-inflammatory-diet-and-adverse-pregnancy-outcomes-circulating-cytokines-and-genomic-imprinting-as-potential-regulators
#16
Lauren E McCullough, Erline E Miller, Laura E Calderwood, Nitin Shivappa, Susan E Steck, Michele R Forman, Michelle Mendez, Rachel Maguire, Bernard F Fuemmeler, Scott H Kollins, Staci Bilbo, Zhiqing Huang, Amy P Murtha, Susan K Murphy, James R Hébert, Cathrine Hoyo
Excessive inflammation during pregnancy alters homeostatic mechanisms of the developing fetus and has been linked to adverse pregnancy outcomes. An anti-inflammatory diet could be a promising avenue to combat the pro-inflammatory state of pregnancy, particularly in obese women, but we lack mechanistic data linking this dietary pattern during pregnancy to inflammation and birth outcomes. In an ethnically diverse cohort of 1057 mother-child pairs, we estimated the relationships between dietary inflammatory potential [measured via the energy-adjusted dietary inflammatory index (E-DII™)] and birth outcomes overall, as well as by offspring sex and maternal pre-pregnancy body mass index (BMI)...
July 5, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28678593/neighborhood-characteristics-influence-dna-methylation-of-genes-involved-in-stress-response-and-inflammation-the-multi-ethnic-study-of-atherosclerosis
#17
Jennifer A Smith, Wei Zhao, Xu Wang, Scott M Ratliff, Bhramar Mukherjee, Sharon L R Kardia, Yongmei Liu, Ava V Diez Roux, Belinda L Needham
Living in a disadvantaged neighborhood is associated with poor health outcomes even after accounting for individual-level socioeconomic factors. The chronic stress of unfavorable neighborhood conditions may lead to dysregulation of the stress reactivity and inflammatory pathways, potentially mediated through epigenetic mechanisms such as DNA methylation. We used multi-level models to examine the relationship between two neighborhood conditions and methylation levels of 18 genes related to stress reactivity and inflammation in purified monocytes from 1,226 participants of the Multi-Ethnic Study of Atherosclerosis (MESA), a population-based sample of US adults...
July 5, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28650214/distinct-dna-methylation-profiles-in-bone-and-blood-of-osteoporotic-and-healthy-postmenopausal-women
#18
Sjur Reppe, Tonje G Lien, Yi-Hsiang Hsu, Vigdis T Gautvik, Ole K Olstad, Rona Yu, Hege G Bakke, Robert Lyle, Marianne K Kringen, Ingrid K Glad, Kaare M Gautvik
DNA methylation affects expression of associated genes and may contribute to the missing genetic effects from genome-wide association studies of osteoporosis. To improve insight into the mechanisms of postmenopausal osteoporosis, we combined transcript profiling with DNA methylation analyses in bone. RNA and DNA were isolated from 84 bone biopsies of postmenopausal donors varying markedly in bone mineral density (BMD). In all, 2529 CpGs in the top 100 genes most significantly associated with BMD were analyzed...
June 26, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28703681/activation-of-gene-expression-by-histone-deubiquitinase-otld1
#19
Ido Keren, Vitaly Citovsky
One of the main mechanisms of epigenetic control is post translational modification of histones, and one of the relatively less characterized, yet functionally important histone modifications is monoubiquitylation, which is reversed by histone deubiquitinases. In Arabidopsis, only two of such enzymes are known to date. One of them, OTLD1, deubiquitylates histone 2B and functions as a transcriptional repressor. But, could the same deubiquitinase act both as a repressor and an activator? Here, we addressed this question...
July 3, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28678648/methylation-of-tmem176a-is-an-independent-prognostic-marker-and-is-involved-in-human-colorectal-cancer-development
#20
Dan Gao, Yingjie Han, Yang Yang, James G Herman, Enqiang Linghu, Qimin Zhan, François Fuks, Zhi John Lu, Mingzhou Guo
Colorectal cancer (CRC) is the third most common malignancy and the fourth most common cause of cancer related death worldwide. This study was designed to find tumor suppressors involved in CRC development by performing RNA-seq. Eight CRC cell lines and 130 cases of primary CRC samples were used. RNA-seq, methylation-specific PCR (MSP), flow cytometry, transwell assays, and a xenograft mouse model were used. Reduction of TMEM176A expression was confirmed in human CRC cells by RNA-seq. TMEM176A was expressed in LS180 and SW620 cells, loss of TMEM176A expression was observed in LOVO, HCT116, RKO, and DLD1 cells, and reduced TMEM176A expression was found in HT29 and SW480 cells...
July 3, 2017: Epigenetics: Official Journal of the DNA Methylation Society
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