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Epigenetics: Official Journal of the DNA Methylation Society

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https://www.readbyqxmd.com/read/29327641/generation-of-an-arrayed-crispr-cas9-library-targeting-epigenetic-regulators-from-high-content-screens-to-in-vivo-assays
#1
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
https://www.readbyqxmd.com/read/29271283/charged-residues-on-the-side-of-the-nucleosome-contribute-to-normal-spt16-gene-interactions-in-budding-yeast
#2
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
https://www.readbyqxmd.com/read/29235940/slc9b1-methylation-predicts-fetal-intolerance-of-labor
#3
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
https://www.readbyqxmd.com/read/29235933/faster-ticking-rate-of-the-epigenetic-clock-is-associated-with-faster-pubertal-development-in-girls
#4
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
https://www.readbyqxmd.com/read/29235923/oncogenic-braf-mutation-induces-dna-methylation-changes-in-a-murine-model-for-human-serrated-colorectal-neoplasia
#5
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
https://www.readbyqxmd.com/read/29235922/dna-methylation-reprogramming-of-human-cancer-cells-by-expression-of-a-plant-5-methylcytosine-dna-glycosylase
#6
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
https://www.readbyqxmd.com/read/29224413/low-hox-gene-expression-in-pml-rar%C3%AE-positive-leukemia-results-from-suppressed-histone-demethylation
#7
Kateřina Rejlová, Alena Musilová, Karolina Škvárová Kramarzová, Markéta Žaliová, Karel Fišer, Meritxell Alberich-Jorda, Jan Trka, Júlia Starková
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 has 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...
December 11, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/29212414/a-suite-of-dna-methylation-markers-that-can-detect-most-common-human-cancers
#8
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...
December 7, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/29166816/tobacco-exposure-related-alterations-in-dna-methylation-and-gene-expression-in-human-monocytes-the-multi-ethnic-study-of-atherosclerosis-mesa
#9
Lindsay M Reynolds, Kurt Lohman, Gary S Pittman, R Graham Barr, Gloria C Chi, Joel Kaufman, Ma Wan, Douglas A Bell, Michael J Blaha, Carlos J Rodriguez, Yongmei Liu
Alterations in DNA methylation and gene expression in blood leukocytes are potential biomarkers of harm and mediators of the deleterious effects of tobacco exposure. However, methodological issues, including the use of self-reported smoking status and mixed cell types have made previously identified alterations in DNA methylation and gene expression difficult to interpret. In this study, we examined associations of tobacco exposure with DNA methylation and gene expression, utilizing a biomarker of tobacco exposure (urine cotinine) and CD14+ purified monocyte samples from 934 participants of the community-based Multi-Ethnic Study of Atherosclerosis (MESA)...
November 23, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/29160764/dna-methylation-profile-in-chronic-myelomonocytic-leukemia-associates-with-distinct-clinical-biological-and-genetic-features
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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