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Epigenetic methylation signature

Linda Witek Janusek, Dina Tell, Noni Gaylord-Harden, Herbert L Mathews
African American men (AAM) who are exposed to trauma and adversity during their early life are at greater risk for poor health over their lifespan. Exposure to adversity during critical developmental windows may embed an epigenetic signature that alters expression of genes that regulate stress response systems, including those genes that regulate the inflammatory response to stress. Such an epigenetic signature may increase risk for diseases exacerbated by inflammation, and may contribute to health disparity...
October 17, 2016: Brain, Behavior, and Immunity
Jiajin Yang, Heng Ge, Caroline J Poulton, Susan L Hogan, Yichun Hu, Britta E Jones, Candace D Henderson, Elizabeth A McInnis, William F Pendergraft, J Charles Jennette, Ronald J Falk, Dominic J Ciavatta
BACKGROUND: Anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) is a systemic autoimmune disease characterized by destructive vascular inflammation. Two prominent ANCA autoantigens are myeloperoxidase (MPO) and proteinase 3 (PR3), and transcription of MPO and PRTN3, the genes encoding the autoantigens, is associated with disease activity. We investigated whether patients with AAV have alterations in histone modifications, particularly those associated with transcriptional activation, at MPO and PRTN3...
2016: Clinical Epigenetics
Raúl Alelú-Paz, Francisco J Carmona, José V Sanchez-Mut, Ariel Cariaga-Martínez, Ana González-Corpas, Nadia Ashour, Maria J Orea, Ana Escanilla, Alfonso Monje, Carmen Guerrero Márquez, Jerónimo Saiz-Ruiz, Manel Esteller, Santiago Ropero
Attempts to discover genes that are involved in the pathogenesis of major psychiatric disorders have been frustrating and often fruitless. Concern is building about the need to understand the complex ways in which nature and nurture interact to produce mental illness. We analyze the epigenome in several brain regions from schizophrenic patients with severe cognitive impairment using high-resolution (450K) DNA methylation array. We identified 139 differentially methylated CpG sites included in known and novel candidate genes sequences as well as in and intergenic sequences which functions remain unknown...
2016: Frontiers in Psychology
Emilio A Herrera, Francisca Cifuentes-Zúñiga, Esteban Figueroa, Cristian Villanueva, Cherie Hernández, René Alegría, Viviana Arroyo, Estefania Peñaloza, Marcelo Farías, Ricardo Uauy, Paola Casanello, Bernardo J Krause
In humans, intrauterine growth restriction (IUGR) is associated with vascular dysfunction, oxidative stress and signs of endothelial programming in umbilical vessels. We aimed to determine the effects of maternal antioxidant treatment with N-acetyl cysteine (NAC) on fetal endothelial function and eNOS programming in IUGR guinea pigs. IUGR was induced by implanting ameroid constrictors on uterine arteries of pregnant guinea pigs at mid gestation, receiving half of the sows NAC in the drinking water (from day 34 until term)...
October 14, 2016: Journal of Physiology
Renaud Massart, Matthew J Suderman, Zsofia Nemoda, Sheila Sutti, Angela M Ruggiero, Amanda M Dettmer, Stephen J Suomi, Moshe Szyf
The effects of social status on human health can be modeled in captive cohorts of nonhuman primates. This study shows that maternal social rank is associated with broad changes in DNA methylation in placentae of rhesus monkeys (N = 10). Differentially methylated genes between social ranks are enriched in signaling pathways playing major roles in placenta physiology. Moreover, the authors found significant overlaps with genes whose expression was previously associated with social rank in adult rhesus monkeys (Tung et al...
October 14, 2016: Child Development
Vincent Huin, Vincent Deramecourt, Dominique Caparros-Lefebvre, Claude-Alain Maurage, Charles Duyckaerts, Eniko Kovari, Florence Pasquier, Valérie Buée-Scherrer, Julien Labreuche, Hélène Behal, Luc Buée, Claire-Marie Dhaenens, Bernard Sablonnière
BACKGROUND: Progressive supranuclear palsy (PSP) is a rare neurodegenerative disease causing parkinsonian symptoms. Altered DNA methylation of the microtubule-associated protein tau gene correlates with the expression changes in Alzheimer's disease and Parkinson's disease brains. However, few studies examine the sequences beyond the constitutive promoter. OBJECTIVES: Because activating different microtubule-associated protein tau gene control regions via methylation might regulate the differential tau expression constituting the specific signatures of individual tauopathies, we compared methylation of a candidate promoter, intron 0...
October 6, 2016: Movement Disorders: Official Journal of the Movement Disorder Society
Oliver Kaut, Ina Schmitt, Jörg Tost, Florence Busato, Yi Liu, Per Hofmann, Stephanie H Witt, Marcella Rietschel, Holger Fröhlich, Ullrich Wüllner
Numerous studies have elucidated the genetics of Parkinson's disease; however, the aetiology of the majority of sporadic cases has not yet been resolved. We hypothesized that epigenetic variations could be associated with PD and evaluated the DNA methylation pattern in PD patients compared to brothers or twins without PD. The methylation of DNA from peripheral blood mononuclear cells of 62 discordant siblings including 24 monozygotic twins was characterized with Illumina DNA Methylation 450K bead arrays and subsequently validated in two independent cohorts: 221 PD vs...
October 6, 2016: Neurogenetics
Wenyi Xu, Fengzhong Wang, Zhongsheng Yu, Fengjiao Xin
Living eukaryotic systems evolve delicate cellular mechanisms for responding to various environmental signals. Among them, epigenetic machinery (DNA methylation, histone modifications, microRNAs, etc.) is the hub in transducing external stimuli into transcriptional response. Emerging evidence reveals the concept that epigenetic signatures are essential for the proper maintenance of cellular metabolism. On the other hand, the metabolite, a main environmental input, can also influence the processing of epigenetic memory...
2016: Genetics & Epigenetics
Yen Ching Lim, Sook Yoong Chia, Shengnan Jin, Weiping Han, Chunming Ding, Lei Sun
OBJECTIVE: DNA methylation may be a stable epigenetic contributor to defining fat cell lineage. METHODS: We performed reduced representation bisulfite sequencing (RRBS) and RNA-seq to depict a genome-wide integrative view of the DNA methylome and transcriptome during brown and white adipogenesis. RESULTS: Our analysis demonstrated that DNA methylation is a stable epigenetic signature for brown and white cell lineage before, during, and after differentiation...
October 2016: Molecular Metabolism
Olivia M de Goede, Pascal M Lavoie, Wendy P Robinson
AIM: To provide insight into fetal nucleated red blood cell (nRBC) development using genome-wide DNA methylation (DNAm) profiling. MATERIALS & METHODS: The DNAm profile (Illumina 450K array) of cord blood (n = 7) derived nRBCs was compared with B cells, CD4 and CD8 T cells, natural killer cells, granulocytes, monocytes and placenta (n = 5). RESULTS: nRBCs and placenta had similarly low array-wide DNAm compared with white blood cells, but their patterns of hypomethylation differed at biologically relevant subsets of the array...
September 30, 2016: Epigenomics
Milan S Geybels, Jonathan L Wright, Marina Bibikova, Brandy Klotzle, Jian-Bing Fan, Shanshan Zhao, Ziding Feng, Elaine A Ostrander, Daniel W Lin, Peter S Nelson, Janet L Stanford
BACKGROUND: Identifying the subset of patients with clinically localized prostate cancer (PCa) at the highest risk of recurrence remains challenging, and better prognostic markers are needed. Gleason score is the best predictor of PCa aggressiveness and prognosis. In the present study, we generated an epigenetic signature based on high versus low Gleason score tumors and evaluated its ability to predict recurrence after radical prostatectomy. METHODS: Genome-wide DNA methylation data from The Cancer Genome Atlas (TCGA; no...
2016: Clinical Epigenetics
Roby Joehanes, Allan C Just, Riccardo E Marioni, Luke C Pilling, Lindsay M Reynolds, Pooja R Mandaviya, Weihua Guan, Tao Xu, Cathy E Elks, Stella Aslibekyan, Hortensia Moreno-Macias, Jennifer A Smith, Jennifer A Brody, Radhika Dhingra, Paul Yousefi, James S Pankow, Sonja Kunze, Sonia Shah, Allan F McRae, Kurt Lohman, Jin Sha, Devin M Absher, Luigi Ferrucci, Wei Zhao, Ellen W Demerath, Jan Bressler, Megan L Grove, Tianxiao Huan, Chunyu Liu, Michael M Mendelson, Chen Yao, Douglas P Kiel, Annette Peters, Rui Wang-Sattler, Peter M Visscher, Naomi R Wray, John M Starr, Jingzhong Ding, Carlos J Rodriguez, Nicholas J Wareham, Marguerite R Irvin, Degui Zhi, Myrto Barrdahl, Paolo Vineis, Srikant Ambatipudi, André G Uitterlinden, Albert Hofman, Joel Schwartz, Elena Colicino, Lifang Hou, Pantel S Vokonas, Dena G Hernandez, Andrew B Singleton, Stefania Bandinelli, Stephen T Turner, Erin B Ware, Alicia K Smith, Torsten Klengel, Elisabeth B Binder, Bruce M Psaty, Kent D Taylor, Sina A Gharib, Brenton R Swenson, Liming Liang, Dawn L DeMeo, George T O'Connor, Zdenko Herceg, Kerry J Ressler, Karen N Conneely, Nona Sotoodehnia, Sharon L R Kardia, David Melzer, Andrea A Baccarelli, Joyce B J van Meurs, Isabelle Romieu, Donna K Arnett, Ken K Ong, Yongmei Liu, Melanie Waldenberger, Ian J Deary, Myriam Fornage, Daniel Levy, Stephanie J London
BACKGROUND: -DNA methylation leaves a long-term signature of smoking exposure and is one potential mechanism by which tobacco exposure predisposes to adverse health outcomes, such as cancers, osteoporosis, lung, and cardiovascular disorders. METHODS AND RESULTS: -To comprehensively determine the association between cigarette smoking and DNA methylation, we conducted a meta-analysis of genome-wide DNA methylation assessed using the Illumina BeadChip 450K array on 15,907 blood derived DNA samples from participants in 16 cohorts (including 2,433 current, 6,518 former, and 6,956 never smokers)...
September 20, 2016: Circulation. Cardiovascular Genetics
Simone Jueliger, John Lyons, Sara Cannito, Illar Pata, Pille Pata, Marianna Shkolnaya, Oriana Lo Re, Marion Peyrou, Francesc Villarroya, Valerio Pazienza, Francesca Rappa, Francesco Cappello, Mohammad Azab, Pietro Taverna, Manlio Vinciguerra
Hepatocellular carcinoma (HCC) is a deadly malignancy characterized at the epigenetic level by global DNA hypomethylation and focal hypermethylation on the promoter of tumor suppressor genes. In most cases it develops on a background of liver steatohepatitis, fibrosis, and cirrhosis. Guadecitabine (SGI-110) is a second-generation hypomethylating agent, which inhibits DNA methyltransferases. Guadecitabine is formulated as a dinucleotide of decitabine and deoxyguanosine that is resistant to cytidine deaminase (CDA) degradation and results in prolonged in vivo exposure to decitabine following small volume subcutaneous administration of guadecitabine...
August 11, 2016: Epigenetics: Official Journal of the DNA Methylation Society
Christine J Huh, Bo Zhang, Matheus B Victor, Sonika Dahiya, Luis Fz Batista, Steve Horvath, Andrew S Yoo
Aging is a major risk factor in many forms of late-onset neurodegenerative disorders. The ability to recapitulate age-related characteristics of human neurons in culture will offer unprecedented opportunities to study the biological processes underlying neuronal aging. Here, we show that using a recently demonstrated microRNA-based cellular reprogramming approach, human fibroblasts from postnatal to near centenarian donors can be efficiently converted into neurons that maintain multiple age-associated signatures...
September 20, 2016: ELife
Maja Klosinska, Colette L Picard, Mary Gehring
In plants, imprinted gene expression occurs in endosperm seed tissue and is sometimes associated with differential DNA methylation between maternal and paternal alleles(1). Imprinting is theorized to have been selected for because of conflict between parental genomes in offspring(2), but most studies of imprinting have been conducted in Arabidopsis thaliana, an inbred primarily self-fertilizing species that should have limited parental conflict. We examined embryo and endosperm allele-specific expression and DNA methylation genome-wide in the wild outcrossing species Arabidopsis lyrata...
2016: Nature Plants
Charlotte A M Cecil, Rebecca G Smith, Esther Walton, Jonathan Mill, Eamon J McCrory, Essi Viding
Childhood maltreatment is a key risk factor for poor mental and physical health. Recently, variation in epigenetic processes, such as DNA methylation, has emerged as a potential pathway mediating this association; yet, the extent to which different forms of maltreatment may be characterized by unique vs shared epigenetic signatures is currently unknown. In this study, we quantified DNA methylation across the genome in buccal epithelial cell samples from a high-risk sample of inner-city youth (n = 124; age = 16-24; 53% female), 68% of whom reported experiencing at least one form of maltreatment while growing up...
September 13, 2016: Journal of Psychiatric Research
Eduard Ling, Amit Ringel, Ina Sigal-Batikoff, Naim Abu-Freha, Hananya Vaknine, Wledy Friah, Avraham Reshef, Ilia Pinsk, Alexander Fich, Sergio Lamprecht
BACKGROUND/AIM: Cancer-associated fibroblasts (CAFs) play an important role in tumor development and progression. The prevailing consensus favors the view that a specific epigenetic signature underpins the stable CAF phenotype. The aim of the present study was to assess global DNA methylation in CAFs during the adenoma-carcinoma sequence in non-familial sporadic human colorectal cancer (CRC). PATIENTS AND METHODS: Immunohistochemical staining of nuclear 5-methylcytosine (5'-meCyt) was performed in matched samples of colonic tumor tissue and normal colonic mucosa excised from six patients with adenomas and four with adenocarcinomas...
September 2016: Anticancer Research
Yves Renaudineau, Esteban Ballestar
No abstract text is available yet for this article.
October 2016: Nature Reviews. Rheumatology
Kristian Hanghøj, Andaine Seguin, Mikkel Schubert, Tobias Madsen, Jakob Skou Pedersen, Eske Willerslev, Ludovic Orlando
The first epigenomes from archaic hominins (AH) and ancient anatomically modern humans (AMH) have recently been characterized, based, however, on a limited number of samples. The extent to which ancient genome-wide epigenetic landscapes can be reconstructed thus remains contentious. Here, we present epiPALEOMIX, an open-source and user-friendly pipeline that exploits post-mortem DNA degradation patterns to reconstruct ancient methylomes and nucleosome maps from shotgun and/or capture-enrichment data. Applying epiPALEOMIX to the sequence data underlying 35 ancient genomes including AMH, AH, equids and aurochs, we investigate the temporal, geographical and preservation range of ancient epigenetic signatures...
September 13, 2016: Molecular Biology and Evolution
Martin Schlensog, Lara Magnus, Timon Heide, Julian Eschenbruch, Florian Steib, Maximilian Tator, Vera Kloten, Michael Rose, Erik Noetzel, Nadine T Gaisa, Ruth Knüchel, Edgar Dahl
Secreted frizzled related protein 3 (SFRP3) contains a cysteine-rich domain (CRD) that shares homology with Frizzled CRD and regulates WNT signaling. Independent studies showed epigenetic silencing of SFRP3 in melanoma and hepatocellular carcinoma. Moreover, a tumor suppressive function of SFRP3 was shown in androgen-independent prostate and gastric cancer cells. The current study is the first to investigate SFRP3 expression and its potential clinical impact on non-small cell lung carcinoma (NSCLC). WNT signaling components present on NSCLC subtypes were preliminary elucidated by expression data of The Cancer Genome Atlas (TCGA)...
September 13, 2016: Epigenetics: Official Journal of the DNA Methylation Society
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