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Epigenetics: Official Journal of the DNA Methylation Society

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https://www.readbyqxmd.com/read/28426282/emerging-roles-of-macrosatellite-repeats-in-genome-organization-and-disease-development
#1
Gabrijela Dumbovic, Sonia-V Forcales, Manuel Perucho
Abundant repetitive DNA sequences are an enigmatic part of the human genome. Despite increasing evidence on the functionality of DNA repeats, their biological role is still elusive and under frequent debate. Macrosatellites are the largest of the tandem DNA repeats, located on one or multiple chromosomes. The contribution of macrosatellites to genome regulation and human health was demonstrated for the D4Z4 macrosatellite repeat array on chromosome 4q35. Reduced copy number of D4Z4 repeats is associated with local euchromatinization and the onset of facioscapulohumeral muscular dystrophy...
April 20, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28426276/integrative-epigenetic-and-genetic-pan-cancer-somatic-alteration-portraits
#2
Lucas A Salas, Kevin C Johnson, Devin C Koestler, Dylan E O'Sullivan, Brock C Christensen
Genetic and epigenetic alterations are required for carcinogenesis and the mutation burden across tumor types has been investigated. Here, we investigate epigenetic alterations with a novel measure of global DNA methylation dysregulation, the methylation dysregulation index (MDI), across 14 cancer types in The Cancer Genome Atlas (TCGA) database. DNA methylation data-obtained using Illumina HumanMethylation450 BeadChip-was accessed from TCGA. We calculated the MDI in 14 tumor types (n = 5,592 tumors), using adjacent normal tissues (n = 701) from each tumor site...
April 20, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28402695/uhrf2-regulates-local-5-methylcytosine-and-suppresses-spontaneous-seizures
#3
Yidan Liu, Bin Zhang, Xiaoyu Meng, Matthew J Korn, Jack M Parent, Lin-Yu Lu, Xiaochun Yu
The 5-methylcytosine (5mC) modification regulates multiple cellular processes and is faithfully maintained following DNA replication. In addition to DNA methyltransferase (DNMT) family proteins, ubiquitin-like PHD and ring finger domain-containing protein 1 (UHRF1) plays an important role in the maintenance of 5 mC levels. Loss of UHRF1 abolishes 5 mC in cells and leads to embryonic lethality in mice. Interestingly, UHRF1 has a paralog, UHRF2, that has similar sequence and domain architecture, but its biological function is not clear...
April 12, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28387599/novel-insights-into-systemic-autoimmune-rheumatic-diseases-using-shared-molecular-signatures-and-an-integrative-analysis
#4
Marie Hudson, Sasha Bernatsky, Ines Colmegna, Maximilien Lora, Tomi Pastinen, Kathleen Klein Oros, Celia M T Greenwood
We undertook this study to identify DNA methylation signatures of three systemic autoimmune rheumatic diseases (SARDs), namely rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis, compared to healthy controls. Using a careful design to minimize confounding, we restricted our study to subjects with incident disease and performed our analyses on purified CD4(+) T cells, key effector cells in SARD. We identified differentially methylated (using the Illumina Infinium HumanMethylation450 BeadChip array) and expressed (using the Illumina TruSeq stranded RNA-seq protocol) sites between cases and controls, and investigated the biological significance of this SARD signature using gene annotation databases...
April 7, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28387569/associations-between-post-translational-histone-modifications-myelomeningocele-risk-environmental-arsenic-exposure-and-folate-deficiency-among-participants-in-a-case-control-study-in-bangladesh
#5
Jannah Tauheed, Marco Sanchez-Guerra, Jane J Lee, Ligi Paul, Md Omar Sharif Ibne Hasan, Quazi Quamruzzaman, Jacob Selhub, Robert O Wright, David C Christiani, Brent A Coull, Andrea A Baccarelli, Maitreyi Mazumdar
Arsenic exposure may contribute to disease risk in humans through alterations in the epigenome. Previous studies reported that arsenic exposure is associated with changes in plasma histone concentrations. Posttranslational histone modifications have been found to differ between the brain tissue of human embryos with neural tube defects and that of controls. Our objectives were to investigate the relationships between plasma histone 3 levels, history of having an infant with myelomeningocele, biomarkers of arsenic exposure, and maternal folate deficiency...
April 7, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28387568/non-linear-patterns-in-age-related-dna-methylation-may-reflect-cd4-t-cell-differentiation
#6
Nicholas D Johnson, Howard W Wiener, Alicia K Smith, Shota Nishitani, Devin M Absher, Donna K Arnett, Stella Aslibekyan, Karen N Conneely
DNA methylation (DNAm) is an important epigenetic process involved in the regulation of gene expression. While many studies have identified thousands of loci associated with age, few have differentiated between linear and non-linear DNAm trends with age. Non-linear trends could indicate early- or late-life gene regulatory processes. Using data from the Illumina 450K array on 336 human peripheral blood samples, we identified 21 CpG sites that associated with age (P<1.03E-7) and exhibited changing rates of DNAm change with age (P<1...
April 7, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28362134/estrogen-signaling-through-estrogen-receptor-%C3%AE-regulates-dna-methylation-and-its-machinery-in-male-germ-line-in-adult-rats
#7
Kushaan Dumasia, Anita Kumar, Sharvari Deshpande, Nafisa H Balasinor
Estrogen, through its receptors, regulates various aspects of spermatogenesis and male fertility. To understand the roles of estrogen receptors (ERα and ERβ) in male fertility, we have developed in vivo selective ER agonist administration models. Treatment of adult male rats with ERα or ERβ agonist for 60 days decreases fertility and litter size mainly due to increased pre- and post-implantation embryo loss. Since epigenetic mechanisms like DNA methylation play a crucial role in male fertility, we investigated the effects of the ER agonists on DNA methylation in spermatozoa...
March 31, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28358281/dna-methylation-aberrancies-as-a-guide-for-surveillance-and-treatment-of-human-cancers
#8
Gangning Liang, Daniel J Weisenberger
DNA methylation aberrancies are hallmarks of human cancers and are characterized by global DNA hypomethylation of repetitive elements and non-CpG rich regions concomitant with locus-specific DNA hypermethylation. DNA methylation changes may result in altered gene expression profiles, most notably the silencing of tumor suppressors, microRNAs, endogenous retorviruses and tumor antigens due to promoter DNA hypermethylation, as well as oncogene upregulation due to gene-body DNA hypermethylation. Here, we review DNA methylation aberrancies in human cancers, their use in cancer surveillance and the interplay between DNA methylation and histone modifications in gene regulation...
March 30, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28304185/modulation-of-transcription-factor-binding-and-epigenetic-regulation-of-the-mlh1-cpg-island-and-shore-by-polymorphism-rs1800734-in-colorectal-cancer
#9
Andrea J Savio, Bharati Bapat
The MLH1 promoter polymorphism rs1800734 is associated with MLH1 CpG island hypermethylation and expression loss in colorectal cancer (CRC). Conversely, variant rs1800734 is associated with MLH1 shore, but not island, hypomethylation in peripheral blood mononuclear cell DNA. To explore these distinct patterns, MLH1 CpG island and shore methylation was assessed in CRC cell lines stratified by rs1800734 genotype. Cell lines containing the variant A allele demonstrated MLH1 shore hypomethylation compared to wild type (GG)...
March 17, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28300471/decoupling-of-dna-methylation-and-activity-of-intergenic-line-1-promoters-in-colorectal-cancer
#10
Natasha Vafadar-Isfahani, Christina Parr, Lara E McMillan, Juliane Sanner, Zhao Yeo, Stephen Saddington, Oliver Peacock, Hazel A Cruickshanks, Richard R Meehan, Jonathan N Lund, Cristina Tufarelli
Hypomethylation of LINE-1 repeats in cancer has been proposed as the main mechanism behind their activation; this assumption, however, was based on findings from early studies that were biased towards young and transpositionally active elements. Here, we investigate the relationship between methylation of two intergenic, transpositionally inactive LINE-1 elements and expression of the LINE-1 chimeric transcript (LCT) 13 and LCT14 driven by their antisense promoters (L1-ASP). Our data from DNA modification, expression, and 5'RACE analyses suggest that colorectal cancer methylation in the regions analyzed is not always associated with LCT repression...
March 16, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28277979/structural-insight-into-inhibitors-of-flavin-adenine-dinucleotide-dependent-lysine-demethylases
#11
Hideaki Niwa, Takashi Umehara
Until 2004, many researchers believed that protein methylation in eukaryotic cells was an irreversible reaction. However, the discovery of lysine-specific demethylase 1 in 2004 drastically changed this view and the concept of chromatin regulation. Since then, the enzymes responsible for lysine demethylation and their cellular substrates, biological significance, and selective regulation have become major research topics in epigenetics and chromatin biology. Many cell-permeable inhibitors for lysine demethylases have been developed, including both target-specific and nonspecific inhibitors...
February 10, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28165855/genome-wide-dna-methylation-associations-with-spontaneous-preterm-birth-in-us-blacks-findings-in-maternal-and-cord-blood-samples
#12
Xiumei Hong, Ben Sherwood, Christine Ladd-Acosta, Shouneng Peng, Hongkai Ji, Ke Hao, Irina Burd, Tami R Bartell, Guoying Wang, Hui-Ju Tsai, Xin Liu, Yuelong Ji, Anastacia Wahl, Deanna Caruso, Aviva Lee-Parritz, Barry Zuckerman, Xiaobin Wang
Preterm birth (PTB) affects one in six U.S. Black babies. Epigenetics is believed to play a role in PTB; however, only a limited number of epigenetic studies of PTB have been reported, most of which have focused on cord blood DNA methylation (DNAm) and/or were conducted in white populations. Here we conducted, by far, the largest epigenome-wide DNAm analysis in 300 Black women who delivered early spontaneous preterm (sPTB, n = 150) or full-term babies (n = 150) and replicated the findings in an independent set of Black mother-newborn pairs from the Boston Birth Cohort...
February 6, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28358224/erratum
#13
(no author information available yet)
No abstract text is available yet for this article.
April 3, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28277978/targeted-dna-demethylation-in-human-cells-by-fusion-of-a-plant-5-methylcytosine-dna-glycosylase-to-a-sequence-specific-dna-binding-domain
#14
Jara Teresa Parrilla-Doblas, Rafael R Ariza, Teresa Roldán-Arjona
DNA methylation is a crucial epigenetic mark associated to gene silencing, and its targeted removal is a major goal of epigenetic editing. In animal cells, DNA demethylation involves iterative 5mC oxidation by TET enzymes followed by replication-dependent dilution and/or replication-independent DNA repair of its oxidized derivatives. In contrast, plants use specific DNA glycosylases that directly excise 5mC and initiate its substitution for unmethylated C in a base excision repair process. In this work, we have fused the catalytic domain of Arabidopsis ROS1 5mC DNA glycosylase (ROS1_CD) to the DNA binding domain of yeast GAL4 (GBD)...
April 3, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28277977/human-liver-epigenetic-alterations-in-non-alcoholic-steatohepatitis-are-related-to-insulin-action
#15
Vanessa D de Mello, Ashok Matte, Alexander Perfilyev, Ville Männistö, Tina Rönn, Emma Nilsson, Pirjo Käkelä, Charlotte Ling, Jussi Pihlajamäki
Both genetic and lifestyle factors contribute to the risk of non-alcoholic steatohepatitis (NASH). Additionally, epigenetic modifications may also play a key role in the pathogenesis of NASH. We therefore investigated liver DNA methylation, as a marker for epigenetic alterations, in individuals with simple steatosis and NASH, and further tested if these alterations were associated with clinical phenotypes. Liver biopsies obtained from 95 obese individuals (age: 49.5 ± 7.7 years, BMI: 43 ± 5.7 kg/m(2), type 2 diabetes [T2D]: 35) as a wedge biopsy during a Roux-en-Y gastric bypass operation were investigated...
April 3, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28267381/dynamics-of-5-carboxylcytosine-during-hepatic-differentiation-potential-general-role-for-active-demethylation-by-dna-repair-in-lineage-specification
#16
Lara C Lewis, Peggy Cho Kiu Lo, Jeremy M Foster, Nan Dai, Ivan R Corrêa, Paulina M Durczak, Gary Duncan, Ashley Ramsawhook, Guruprasad Padur Aithal, Chris Denning, Nicholas R F Hannan, Alexey Ruzov
Patterns of DNA methylation (5-methylcytosine, 5mC) are rearranged during differentiation contributing to the regulation of cell type-specific gene expression. TET proteins oxidize 5mC to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). Both 5fC and 5caC can be recognized and excised from DNA by thymine-DNA glycosylase (TDG) followed by the subsequent incorporation of unmodified cytosine into the abasic site via the base excision repair (BER) pathway. We previously demonstrated that 5caC accumulates during lineage specification of neural stem cells (NSCs) suggesting that such active demethylation pathway is operational in this system; however, it is still unknown if TDG/BER-dependent demethylation is used during other types of cellular differentiation...
April 3, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28128679/early-life-stress-links-5-hydroxymethylcytosine-to-anxiety-related-behaviors
#17
Ligia A Papale, Andy Madrid, Sisi Li, Reid S Alisch
Environmental stress contributes to the development of psychiatric disorders, including posttraumatic stress disorder and anxiety. While even acute stress alters gene expression, the molecular mechanisms underlying these changes remain largely unknown. 5-hydroxymethylcytosine (5hmC) is a novel environmentally sensitive DNA modification that is highly enriched in the brain and is associated with active transcription of neuronal genes. Here we examined behavioral and molecular alterations in adult mice that experienced an early-life stress before weaning (postnatal day 12 to 18) and found anxiety-like behaviors in adult female mice that were accompanied by correlated disruptions of hypothalamic 5hmC and gene expression in 118 genes, revealing potentially functional 5hmC (i...
April 3, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28106509/potential-epigenetic-biomarkers-of-obesity-related-insulin-resistance-in-human-whole-blood
#18
Samantha E Day, Richard L Coletta, Joon Young Kim, Luis A Garcia, Latoya E Campbell, Tonya R Benjamin, Lori R Roust, Elena A De Filippis, Lawrence J Mandarino, Dawn K Coletta
Obesity can increase the risk of complex metabolic diseases, including insulin resistance. Moreover, obesity can be caused by environmental and genetic factors. However, the epigenetic mechanisms of obesity are not well defined. Therefore, the identification of novel epigenetic biomarkers of obesity allows for a more complete understanding of the disease and its underlying insulin resistance. The aim of our study was to identify DNA methylation changes in whole-blood that were strongly associated with obesity and insulin resistance...
April 3, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28059604/valentin-haecker-1864-1927-as-a-pioneer-of-phenogenetics-building-the-bridge-between-genotype-and-phenotype
#19
Uwe Hoßfeld, Elizabeth Watts, Georgy S Levit
Valentin Haecker is one of the forerunners of experimental biology, genetics, and developmental physiology. Haecker introduced the term Phänogenetik (phenogenetics) in 1918 in Entwicklungsgeschichtliche Eigenschaftsanalyse (Evolutionary Analysis of Characters), in which he described the earliest stages in the development of the phenotype. (1) His major objective in this publication was to integrate the 2 most important concepts of Mendelian genetics-phenotype and genotype-within a well-articulated theory. Haecker realized that a proper analysis of how the genotype gives rise to the phenotype requires the integration of knowledge of morphology, physiology, and experimental embryology...
April 3, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28165867/hypermethylated-ltr-retrotransposon-exhibits-enhancer-activity
#20
Tianxiang Hu, Xingguo Zhu, Wenhu Pi, Miao Yu, Huidong Shi, Dorothy Tuan
LTR retrotransposons are repetitive DNA elements comprising ∼10% of the human genome. They are silenced by hypermethylation of cytosines in CpG dinucleotides and are considered parasitic DNA serving no useful function for the host genome. However, hypermethylated LTRs contain enhancer and promoter sequences and can promote tissue-specific transcription of cis-linked genes. To resolve the apparent paradox of hypermethylated LTRs possessing transcriptional activities, we studied the ERV-9 LTR retrotransposon located at the 5' border of the transcriptionally active β-globin gene locus in human erythroid progenitor and erythroleukemia K562 cells...
March 4, 2017: Epigenetics: Official Journal of the DNA Methylation Society
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