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Epigenetics: Official Journal of the DNA Methylation Society

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https://www.readbyqxmd.com/read/29160764/dna-methylation-profile-in-chronic-myelomonocytic-leukemia-associates-with-distinct-clinical-biological-and-genetic-features
#1
Laura Palomo, Roberto Malinverni, Marta Cabezón, Blanca Xicoy, Montserrat Arnan, Rosa Coll, Helena Pomares, Olga García, Francisco Fuster-Tormo, Javier Grau, Evarist Feliu, Francesc Solé, Marcus Buschbeck, Lurdes Zamora
Chromosomal abnormalities are detected in 20-30% of patients with chronic myelomonocytic leukemia (CMML) and correlate with prognosis. On the mutation level, disruptive alterations are particularly frequent in chromatin regulatory genes. However, little is known about the consequential alterations in the epigenetic marking of the genome. Here, we report the analysis of genomic DNA methylation patterns of 64 CMML patients and 10 healthy controls, using a DNA methylation microarray focused on promoter regions...
November 21, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/29160179/the-miage-calculator-a-dna-methylation-based-mitotic-age-calculator-of-human-tissue-types
#2
Ahrim Youn, Shuang Wang
Cell division is important in human aging and cancer. To estimate the number of cell divisions (mitotic age) of a given tissue type between individuals is of great interest as that not only allows to study biological aging using a new molecular aging target but also allows the stratification of prospective cancer risk. Here we introduce the MiAge Calculator, a mitotic age calculator based on a novel statistical framework, the MiAge model. MiAge is designed to quantitatively estimate mitotic age (total number of lifetime cell divisions) of a tissue using the stochastic replication errors accumulated in the epigenetic inheritance process during cell divisions...
November 21, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/29160132/active-h3k27me3-demethylation-by-kdm6b-is-required-for-normal-development-of-bovine-preimplantation-embryos
#3
Nhi Chung, Yanina S Bogliotti, Wei Ding, Marcela Vilarino, Kazuki Takahashi, James L Chitwood, Richard M Schultz, Pablo J Ross
The substantial epigenetic remodeling that occurs during early stages of mammalian embryonic development likely contributes to reprogramming the parental genomes from a differentiated to a totipotent state and activation of the embryonic genome. Trimethylation of lysine 27 of histone 3 (H3K27me3) is a repressive mark that undergoes global dynamic changes during preimplantation development of several species. To ascertain the role of H3K27me3 in bovine preimplantation development we perturbed the activity of KDM6B, which demethylates H3K27me3...
November 21, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/29160127/the-fetal-programming-effect-of-prenatal-smoking-on-igf1r-and-igf1-methylation-is-organ-and-sex-specific
#4
Karolin F Meyer, Rikst Nynke Verkaik-Schakel, Wim Timens, Lester Kobzik, Torsten Plösch, Machteld N Hylkema
The impact of prenatal smoke exposure (PSE) on DNA methylation has been demonstrated in blood samples from children of smoking mothers, but evidence for sex-dependent smoke-induced effects is limited. As the identified differentially methylated genes can be associated with developmental processes, and insulin-like growth factors (IGFs) play a critical role in prenatal tissue growth, we hypothesized that PSE induces fetal programming of Igf1r and Igf1. Using a mouse model of smoking during pregnancy, we show that PSE alters promoter methylation of Igf1r and Igf1 and deregulates their gene expression in lung and liver of fetal (E17...
November 21, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/29111854/the-effect-of-morphine-upon-dna-methylation-in-ten-regions-of-the-rat-brain
#5
Timothy M Barrow, Hyang-Min Byun, Xinyan Li, Chris Smart, Yong-Xiang Wang, Yacong Zhang, Andrea A Baccarelli, Liqiong Guo
Morphine is one of the most effective analgesics in medicine. However, its use is associated with the development of tolerance and dependence. Recent studies demonstrating epigenetic changes in the brain after exposure to opiates have provided insight into mechanisms possibly underlying addiction. In this study, we sought to identify epigenetic changes in ten regions of the rat brain following acute and chronic morphine exposure. We analyzed DNA methylation of six nuclear-encoded genes implicated in brain function (Bdnf, Comt, Il1b, Il6, Nr3c1, and Tnf) and three mitochondrially-encoded genes (Mtco1, Mtco2, and Mtco3), and measured global 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) levels...
November 7, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/29099289/trichostatin-a-decreases-the-levels-of-mecp2-expression-and-phosphorylation-and-increases-its-chromatin-binding-affinity
#6
Katrina V Good, Alexia Martínez de Paz, Monica Tyagi, Manjinder S Cheema, Anita A Thambirajah, Taylor L Gretzinger, Gilda Stefanelli, Bob Chow, Oliver Krupke, Michael Hendzel, Kristal Missiaen, Alan Underhill, Nicoletta Landsberger, Juan Ausió
MeCP2 binds to methylated DNA in a chromatin context and has an important role in cancer and brain development and function. Histone deacetylase (HDAC) inhibitors are currently being used to palliate many cancer and neurological disorders. Yet, the molecular mechanisms involved are not well known for the most part and, in particular, the relationship between histone acetylation and MeCP2 is not well understood. In this paper, we study the effect of the HDAC inhibitor trichostatin A (TSA) on MeCP2, a protein whose dysregulation plays an important role in these diseases...
November 3, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/29099287/pax5-gene-as-a-novel-methylation-marker-that-predicts-both-clinical-outcome-and-cisplatin-sensitivity-in-esophageal-squamous-cell-carcinoma
#7
Keisuke Kurimoto, Masamichi Hayashi, Rafael Guerrero-Preston, Masahiko Koike, Mitsuro Kanda, Sho Hirabayashi, Hiroshi Tanabe, Nao Takano, Naoki Iwata, Yukiko Niwa, Hideki Takami, Daisuke Kobayashi, Chie Tanaka, Suguru Yamada, Goro Nakayama, Hiroyuki Sugimoto, Tsutomu Fujii, Michitaka Fujiwara, Yasuhiro Kodera
Therapeutic strategies for esophageal cancer largely depend on histopathological assessment. To select appropriate treatments for individual patients, we examined the background molecular characteristics of tumor malignancy and sensitivity to multidisciplinary therapy. Seventy-eight surgically-resected esophageal squamous cell carcinoma (ESCC) cases during 2001-2013 were examined. PAX5, a novel gene methylation marker in ESCC, was evaluated in the specimens, as methylation of this gene was identified as an extremely tumor-specific event in squamous cell carcinogenesis of head and neck...
November 3, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/29099285/critical-roles-of-protein-methyltransferases-and-demethylases-in-the-regulation-of-embryonic-stem-cell-fate
#8
Theodore Vougiouklakis, Yusuke Nakamura, Vassiliki Saloura
Accumulating evidence has recently shown that protein methyltransferases and demethylases are crucial regulators in either maintaining pluripotent states or inducing differentiation of embryonic stem cells. These enzymes control pluripotent signatures by mediating activation or repression of histone marks, or through direct methylation of non-histone proteins. Importantly, chromatin modifiers can influence the fate of many differentiation-related genes by loosening chromatin and allowing for transcriptional activation of lineage-specific genes...
November 3, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/29099283/lowly-methylated-region-analysis-identifies-ebf1-as-a-potential-epigenetic-modifier-in-breast-cancer
#9
Nora Fernandez-Jimenez, Athena Sklias, Szilvia Ecsedi, Vincent Cahais, Davide Degli-Esposti, Antonin Jay, Pierre Benoit Ancey, Hae Dong Woo, Hector Hernandez-Vargas, Zdenko Herceg
Breast cancer (BC) encompasses heterogeneous pathologies with different subtypes exhibiting distinct molecular changes, including those related to DNA methylation. However, the role of these changes in mediating BC heterogeneity is poorly understood. Lowly methylated regions (LMRs), non-CpG island loci that usually contain transcription factor (TF) binding sites, have been suggested to act as regulatory elements that define cellular identity. In this study, we aimed to identify the key subtype-specific TFs that may lead to LMR generation and shape the BC methylome and transcription program...
November 3, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/29099282/dna-methylation-and-obesity-traits-an-epigenome-wide-association-study-the-regicor-study
#10
Sergi Sayols-Baixeras, Isaac Subirana, Alba Fernández-Sanlés, Mariano Sentí, Carla Lluís-Ganella, Jaume Marrugat, Roberto Elosua
Obesity is associated with increased risk of several diseases and has become epidemic. Obesity is highly heritable but the genetic variants identified by genome-wide association studies explain only limited variability. Epigenetics could contribute to explain the missing variability. The study aim was to discover differential methylation patterns related to obesity. We designed an epigenome-wide association study with a discovery phase in a subsample of 641 REGICOR study participants, validated by analysis of 2,515 participants in the Framingham Offspring Study...
November 3, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/29099281/variability-of-genome-wide-dna-methylation-and-mrna-expression-profiles-in-reproductive-and-endocrine-disease-related-tissues
#11
Nilufer Rahmioglu, Alexander W Drong, Helen Lockstone, Thomas Tapmeier, Karin Hellner, Merli Saare, Triin Laisk-Podar, Christine Dew, Emily Tough, George Nicholson, Maire Peters, Andrew P Morris, Cecilia M Lindgren, Christian M Becker, Krina T Zondervan
Genome-wide association studies in the fields of reproductive medicine and endocrinology are yielding robust genetic variants associated with disease. Integrated genomic, transcriptomic, and epigenomic molecular profiling studies are common methodologies used to understand the biological pathways perturbed by these variants. However, molecular profiling resources do not include the tissue most relevant to many female reproductive traits, the endometrium, while the parameters influencing variability of results from its molecular profiling are unclear...
November 3, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/29099280/variant-histone-h2afv-reprograms-dna-methylation-during-early-zebrafish-development
#12
Bhavani Madakashira, Laura Corbett, Chi Zhang, Pier Paoli, John W Casement, Jelena Mann, Kirsten C Sadler, Derek A Mann
The DNA methylome is re-patterned during discrete phases of vertebrate development. In zebrafish, there are two waves of global DNA demethylation and re-methylation: the first occurs prior to gastrulation when the parental methylome is changed to the zygotic pattern and the second occurs after formation of the embryonic body axis, during organ specification. The occupancy of the histone variant H2A.Z and regions of DNA methylation are generally anti-correlated, and it has been proposed that H2A.Z restricts the boundaries of highly methylated regions...
November 3, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/29099276/setdb2-and-riox2-are-differentially-expressed-among-renal-cell-tumor-subtypes-associating-with-prognosis-and-metastization
#13
Maria João Ferreira, Ana Sílvia Pires-Luís, Márcia Vieira-Coimbra, Pedro Costa-Pinheiro, Luís Antunes, Paula C Dias, Francisco Lobo, Jorge Oliveira, Céline S Gonçalves, Bruno M Costa, Rui Henrique, Carmen Jerónimo
Increasing detection of small renal masses by imaging techniques entails the need for accurate discrimination between benign and malignant renal cell tumors (RCTs) as well as among malignant RCTs, owing to differential risk of progression through metastization. Although histone methylation has been implicated in renal tumorigenesis, its potential as biomarker for renal cell carcinoma (RCC) progression remains largely unexplored. Thus, we aimed to characterize the differential expression of histone methyltransferases (HMTs) and histone demethylases (HDMs) in RCTs to assess their potential as metastasis biomarkers...
November 3, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/29099274/causes-of-blood-methylomic-variation-for-middle-aged-women-measured-by-the-humanmethylation450-array
#14
Shuai Li, Ee Ming Wong, Tuong L Nguyen, Ji-Hoon Eric Joo, Jennifer Stone, Gillian S Dite, Graham G Giles, Richard Saffery, Melissa C Southey, John L Hopper
To address the limitations in current classic twin/family research on the genetic and/or environmental causes of human methylomic variation, we measured blood DNA methylation for 479 women (mean age 56 years) including 66 monozygotic (MZ), 66 dizygotic (DZ) twin pairs and 215 sisters of twins, and 11 random technical duplicates using the HumanMethylation450 array. For each methylation site, we estimated the correlation for pairs of duplicates, MZ twins, DZ twins, and siblings, fitted variance component models by assuming the variation is explained by genetic factors, by shared and individual environmental factors, and by independent measurement error, and assessed the best fitting model...
November 3, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/29099273/dna-methylation-profiles-in-sibling-pairs-discordant-for-intrauterine-exposure-to-maternal-gestational-diabetes
#15
Eunae Kim, Soo Heon Kwak, Hye Rim Chung, Jung Hun Ohn, Jae Hyun Bae, Sung Hee Choi, Kyong Soo Park, Joon-Seok Hong, Joohon Sung, Hak Chul Jang
Intrauterine exposure to hyperglycemia is reported to confer increased metabolic risk in later life, supporting the 'developmental origins of health and disease' hypothesis. Epigenetic alterations are suggested as one of the possible underlying mechanisms. In this study, we compared pairwise DNA methylation differences between siblings whose intrauterine exposure to maternal gestational diabetes (GDM) were discordant. Methylation of peripheral blood DNA of 18 sibling pairs was measured using Infinium HumanMethylation450 BeadChip assays...
November 3, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28949791/estrogen-through-estrogen-receptor-1-regulates-histone-modifications-and-chromatin-remodeling-during-spermatogenesis-in-adult-rats
#16
Kushaan Dumasia, Anita Kumar, Sharvari Deshpande, Nafisa H Balasinor
Estrogen receptors (ESR1 and ESR2) play crucial roles in various processes during spermatogenesis. To elucidate individual roles of ESRs in male fertility, we developed in vivo selective ESR agonist administration models. Adult male rats treated with ESR1 and ESR2 agonist for 60 days show spermatogenic defects leading to reduced sperm counts and fertility. While studying epigenetic changes in the male germ line that could have affected fertility, we earlier observed a decrease in DNA methylation and its machinery upon ESR2 agonist treatment...
September 26, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28945496/mouse-olfactory-bulb-methylome-and-hydroxymethylome-maps-reveal-noncanonical-active-turnover-of-dna-methylation
#17
Qin Ma, Huan Lu, Ziying Xu, Yuanyuan Zhou, Weimin Ci
Hydroxylation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) by TET enzymes presents a particular regulatory mechanism in the mammalian brain. However, although methylation and hydroxymethylation of cytosines in non-CpG contexts have been reported, these mechanisms remain poorly understood. Here, we applied TAB-seq and oxBS-seq selectively to detect 5hmC and 5mC at base resolution in olfactory bulb derived from female mice. We found that active turnover of 5mC to 5hmC occurred in both CpG and non-CpG contexts...
September 25, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28933651/characterization-of-h3-3k36m-as-a-tool-to-study-h3k36-methylation-in-cancer-cells
#18
Saumya M Sankaran, Or Gozani
Recurrent mutations at key lysine residues in the histone variant H3.3 are thought to play an etiologic role in the development of distinct subsets of pediatric gliomas and bone and cartilage cancers. H3.3K36M is one such mutation that was originally identified in chondroblastomas, and its expression in these tumors contributes to oncogenic reprogramming by triggering global depletion of dimethylation and trimethylation at H3K36 with a concomitant increase in the levels of H3K27 trimethylation. H3.3K36M expression can also cause epigenomic changes in cell types beyond chondrocytic cells...
September 21, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28933623/the-defining-dna-methylation-signature-of-kabuki-syndrome-enables-functional-assessment-of-genetic-variants-of-unknown-clinical-significance
#19
Erfan Aref-Eshghi, Laila C Schenkel, Hanxin Lin, Cindy Skinner, Peter Ainsworth, Guillaume Paré, David Rodenhiser, Charles Schwartz, Bekim Sadikovic
Kabuki syndrome (KS) is caused by mutations in KMT2D, which is a histone methyltransferase involved in methylation of H3K4, a histone marker associated with DNA methylation. Analysis of >450,000 CpGs in 24 KS patients with pathogenic mutations in KMT2D and 216 controls, identified several genomic regions, along with 1,504 CpG sites with significant DNA methylation changes including a number of Hox genes and the MYO1F gene. Using the most differentiating and significant probes and regions we developed a "methylation variant pathogenicity (MVP) score," which enables 100% sensitive and specific identification of individuals with KS, which was confirmed using multiple public and internal patient DNA methylation databases...
September 21, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28933600/a-novel-acetyltransferase-p300-inhibitor-ameliorates-hypertension-associated-cardio-renal-fibrosis
#20
Rahul Rai, Suresh K Verma, David Kim, Veronica Ramirez, Elizabeth Lux, Chengjin Li, Susmita Sahoo, Lisa D Wilsbacher, Douglas E Vaughan, Susan E Quaggin, Asish K Ghosh
Hypertension-associated end-organ damage commonly leads to cardiac and renal fibrosis. As no effective anti-fibrotic therapy currently exists, the unchecked progression of fibrogenesis manifests as cardio-renal failure and early death. We have previously shown that FATp300-p300 with intrinsic factor acetyltransferase activity-is an essential epigenetic regulator of fibrogenesis, and is elevated in several fibrotic tissues. In this report, we investigate the therapeutic efficacy of a novel FATp300 inhibitor, L002, in a murine model of hypertensive cardio-renal fibrosis...
September 21, 2017: Epigenetics: Official Journal of the DNA Methylation Society
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