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Epigenetic methylation signature

Srijaya Thekkeparambil Chandrabose, Sandhya Sriram, Subha Subramanian, Shanshan Cheng, Wee Kiat Ong, Steve Rozen, Noor Hayaty Abu Kasim, Shigeki Sugii
BACKGROUND: While a shift towards non-viral and animal component-free methods of generating induced pluripotent stem (iPS) cells is preferred for safer clinical applications, there is still a shortage of reliable cell sources and protocols for efficient reprogramming. METHODS: Here, we show a robust episomal and xeno-free reprogramming strategy for human iPS generation from dental pulp stem cells (DPSCs) which renders good efficiency (0.19%) over a short time frame (13-18 days)...
March 20, 2018: Stem Cell Research & Therapy
Maria Giulia Bacalini, Claudio Franceschi, Davide Gentilini, Francesco Ravaioli, Xiaoyuan Zhou, Daniel Remondini, Chiara Pirazzini, Cristina Giuliani, Elena Marasco, Noémie Gensous, Anna Maria Di Blasio, Ewa Ellis, Roberto Gramignoli, Gastone Castellani, Miriam Capri, Stephen Strom, Christine Nardini, Matteo Cescon, Gian Luca Grazi, Paolo Garagnani
The feasibility of liver transplantation from old healthy donors suggests that this organ is able to preserve its functionality during aging. To explore the biological basis of this phenomenon, we characterized the epigenetic profile of liver biopsies collected from 45 healthy liver donors ranging from 13 to 90 years old using the Infinium HumanMethylation450 BeadChip. The analysis indicates that a large remodeling in DNA methylation patterns occurs, with 8823 age-associated differentially methylated CpG probes...
March 15, 2018: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
Antonio Fadda, Davide Gentilini, Loredana Moi, Ludovic Barault, Vera Piera Leoni, Pia Sulas, Luigi Zorcolo, Angelo Restivo, Francesco Cabras, Federica Fortunato, Cesare Zavattari, Liliana Varesco, Viviana Gismondi, Maria Rosaria De Miglio, Antonio Mario Scanu, Federica Colombi, Pasquale Lombardi, Ivana Sarotto, Eleonora Loi, Francesco Leone, Silvia Giordano, Federica Di Nicolantonio, Amedeo Columbano, Patrizia Zavattari
Colorectal cancer (CRC) develops through the accumulation of both genetic and epigenetic alterations. However, while the former are already used as prognostic and predictive biomarkers, the latter are less well characterized. Here, performing global methylation analysis on both CRCs and adenomas by Illumina Infinium HumanMethylation450 Bead Chips, we identified a panel of 74 altered CpG islands, demonstrating that the earliest methylation alterations affect genes coding for proteins involved in the crosstalk between cell and surrounding environment...
March 15, 2018: International Journal of Cancer. Journal International du Cancer
Tim S Nawrot, Nelly D Saenen, Julie Schenk, Bram G Janssen, Valeria Motta, Letizia Tarantini, Bianca Cox, Wouter Lefebvre, Charlotte Vanpoucke, Cristina Maggioni, Valentina Bollati
In mammals, a central clock maintains the daily rhythm in accordance with the external environment. At the molecular level, the circadian rhythm is maintained by epigenetic regulation of the Circadian pathway. Here, we tested the role of particulate matter with an aerodynamic diameter ≤ 2.5 μm (PM2.5 ) exposure during gestational life on human placental Circadian pathway methylation, as an important molecular target for healthy development. In 407 newborns, we quantified placental methylation of CpG sites within the promoter regions of the following genes: CLOCK, BMAL1, NPAS2, CRY1-2 and PER1-3 using bisulfite-PCR-pyrosequencing...
March 7, 2018: Environment International
Sloane K Tilley, Elizabeth M Martin, Lisa Smeester, Robert M Joseph, Karl C K Kuban, Tim C Heeren, Olaf U Dammann, T Michael O'Shea, Rebecca C Fry
BACKGROUND: The placenta is the central regulator of maternal and fetal interactions. Perturbations of placental structure and function have been associated with adverse neurodevelopmental outcomes later in life. Placental CpG methylation represents an epigenetic modification with the potential to impact placental function, fetal development and child health later in life. STUDY DESIGN: Genome-wide placental CpG methylation levels were compared between spontaneous versus indicated deliveries from extremely preterm births (EPTBs) (n = 84)...
2018: PloS One
Timothy G Jenkins, Lihua Liu, Kenneth I Aston, Douglas T Carrell
Sperm epigenetic profiles are frequently studied and are of great interest in many fields. One major technical concern when assessing these marks is the potential for somatic cell contamination. Because somatic cells have dramatically different epigenetic signatures, even small levels of contamination can result in significant problems in analysis and interpretation of data. In this study we evaluate an assay, which we designed to offer a reliable 'pre-screen' for somatic cell contamination that directly assesses the DNA being used in the study to determine tissue purity...
April 2018: Systems Biology in Reproductive Medicine
Alexander Beck, Franziska Trippel, Alexandra Wagner, Saskia Joppien, Max Felle, Christian Vokuhl, Thomas Schwarzmayr, Tim M Strom, Dietrich von Schweinitz, Gernot Längst, Roland Kappler
Background: Hepatoblastoma (HB) is the most common liver tumor of childhood and occurs predominantly within the first 3 years of life. In accordance to its early manifestation, HB has been described to display an extremely low mutation rate. As substitute, epigenetic modifiers seem to play an exceptional role in its tumorigenesis, which holds promise to develop targeted therapies and establish biomarkers for patient risk stratification. Results: We examined the role of a newly described protein complex consisting of three epigenetic regulators, namely E3 ubiquitin-like containing PHD and RING finger domain 1 (UHRF1), ubiquitin-specific-processing protease 7 (USP7), and DNA methyltransferase 1 (DNMT1), in HB...
2018: Clinical Epigenetics
A Zullo, E Simone, M Grimaldi, M Gagliardi, L Zullo, M R Matarazzo, F P Mancini
BACKGROUND AND AIM: Over the last decades advances in understanding the molecular bases of the close relationship between nutrition, metabolism, and diseases have been impressive. However, there are always novel frontiers coming up and epigenetics is one of these. Sirtuins, are pivotal factors in the control of metabolic pathways according to nutrient availability. In the present study we evaluated the effect of nutrient deprivation on expression, DNA methylation and chromatin status of the sirtuin genes...
February 13, 2018: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
Hyerim Kim, Xudong Wang, Peng Jin
An emerging paradigm shift for disease diagnosis is to rely on molecular characterization beyond traditional clinical and symptom-based examinations. Although genetic alterations and transcription signature were first introduced as potential biomarkers, clinical implementations of these markers are limited due to low reproducibility and accuracy. Instead, epigenetic changes are considered as an alternative approach to disease diagnosis. Complex epigenetic regulation is required for normal biological functions and it has been shown that distinctive epigenetic disruptions could contribute to disease pathogenesis...
February 17, 2018: Journal of Genetics and Genomics, Yi Chuan Xue Bao
Cheng-Jian Xu, Cilla Söderhäll, Mariona Bustamante, Nour Baïz, Olena Gruzieva, Ulrike Gehring, Dan Mason, Leda Chatzi, Mikel Basterrechea, Sabrina Llop, Maties Torrent, Francesco Forastiere, Maria Pia Fantini, Karin C Lødrup Carlsen, Tari Haahtela, Andréanne Morin, Marjan Kerkhof, Simon Kebede Merid, Bianca van Rijkom, Soesma A Jankipersadsing, Marc Jan Bonder, Stephane Ballereau, Cornelis J Vermeulen, Raul Aguirre-Gamboa, Johan C de Jongste, Henriette A Smit, Ashish Kumar, Göran Pershagen, Stefano Guerra, Judith Garcia-Aymerich, Dario Greco, Lovisa Reinius, Rosemary R C McEachan, Raf Azad, Vegard Hovland, Petter Mowinckel, Harri Alenius, Nanna Fyhrquist, Nathanaël Lemonnier, Johann Pellet, Charles Auffray, Pieter van der Vlies, Cleo C van Diemen, Yang Li, Cisca Wijmenga, Mihai G Netea, Miriam F Moffatt, William O C M Cookson, Josep M Anto, Jean Bousquet, Tiina Laatikainen, Catherine Laprise, Kai-Håkon Carlsen, Davide Gori, Daniela Porta, Carmen Iñiguez, Jose Ramon Bilbao, Manolis Kogevinas, John Wright, Bert Brunekreef, Juha Kere, Martijn C Nawijn, Isabella Annesi-Maesano, Jordi Sunyer, Erik Melén, Gerard H Koppelman
BACKGROUND: DNA methylation profiles associated with childhood asthma might provide novel insights into disease pathogenesis. We did an epigenome-wide association study to assess methylation profiles associated with childhood asthma. METHODS: We did a large-scale epigenome-wide association study (EWAS) within the Mechanisms of the Development of ALLergy (MeDALL) project. We examined epigenome-wide methylation using Illumina Infinium Human Methylation450 BeadChips (450K) in whole blood in 207 children with asthma and 610 controls at age 4-5 years, and 185 children with asthma and 546 controls at age 8 years using a cross-sectional case-control design...
February 26, 2018: Lancet Respiratory Medicine
Agatha Schlüter, Juan Sandoval, Stéphane Fourcade, Angel Díaz-Lagares, Montserrat Ruiz, Patrizia Casaccia, Manel Esteller, Aurora Pujol
Epigenomic changes may either cause disease or modulate its expressivity, adding a layer of complexity to mendelian diseases. X-linked adrenoleukodystrophy (X-ALD) is a rare neurometabolic condition exhibiting discordant phenotypes, ranging from a childhood cerebral inflammatory demyelination (cALD) to an adult-onset mild axonopathy in spinal cords (AMN). The AMN form may occur with superimposed inflammatory brain demyelination (cAMN). All patients harbor loss of function mutations in the ABCD1 peroxisomal transporter of very-long chain fatty acids...
February 24, 2018: Brain Pathology
Ying Wang, Xiaoxi Huang, Dong Leng, Jifeng Li, Lei Wang, Yan Liang, Jun Wang, Ran Miao, Tao Jiang
Chronic thromboembolic pulmonary hypertension (CTEPH) is a life-threatening disease which is often underpinned by vascular remodeling. Although pulmonary arterial smooth muscle cells (PASMCs) are the main participants in vascular remodeling, their biological role in CTEPH is not entirely clear. In this study, we analyzed the whole epigenome-wide DNA methylation profiles of cultured PASMCs from CTEPH and control cell lines using an Illumina HumanMethylation450K BeadChip. A total of 6829 significantly differentially methylated probes (DMPs) were detected between the two groups, of which 4246 DMPs were hypermethylated while 2583 DMPs were hypomethylated...
February 23, 2018: Physiological Genomics
Jennifer Blaze, Jun Wang, Lap Ho, Natalia Mendelev, Fatemeh Haghighi, Giulio Maria Pasinetti
SCOPE: Stress is a known contributor to various forms of disease in humans and animals, although mechanisms are still unknown. In animals, psychosocial stress-induced depression/anxiety phenotypes are coincidental with increased inflammation in both brain and blood. We recently showed that a novel treatment with a select bioactive polyphenol preparation promotes resilience to stress-mediated depression/anxiety phenotypes mice. Moreover, we identified selective bioactive phenolic compounds within the polyphenol preparation that were effective in mitigating the behavioral effects of bone marrow transplantation from stressed mice...
February 22, 2018: Molecular Nutrition & Food Research
Matteo Zampini, Claudia Tregnago, Valeria Bisio, Luca Simula, Giulia Borella, Elena Manara, Carlo Zanon, Francesca Zonta, Valentina Serafin, Benedetta Accordi, Silvia Campello, Barbara Buldini, Andrea Pession, Franco Locatelli, Giuseppe Basso, Martina Pigazzi
The somatic translocation t(8;21)(q22;q22)/RUNX1-RUNX1T1 is one of the most frequent rearrangements found in children with standard-risk acute myeloid leukemia (AML). Despite the favorable prognostic role of this aberration, we recently observed a higher than expected frequency of relapse. Here, we employed an integrated high-throughput approach aimed at identifying new biological features predicting relapse among 34 t(8;21)-rearranged patients. We found that the DNA methylation status of patients who suffered from relapse was peculiarly different from that of children maintaining complete remission...
February 2, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Kristin Freudenberg, Nadja Lindner, Sebastian Dohnke, Annette I Garbe, Sonja Schallenberg, Karsten Kretschmer
Under physiological conditions, CD4+ regulatory T (Treg) cells expressing the transcription factor Foxp3 are generated in the thymus [thymus-derived Foxp3+ Treg (tTregs) cells] and extrathymically at peripheral sites [peripherally induced Foxp3+ Treg (pTreg) cell], and both developmental subsets play non-redundant roles in maintaining self-tolerance throughout life. In addition, a variety of experimental in vitro and in vivo modalities can extrathymically elicit a Foxp3+ Treg cell phenotype in peripheral CD4+ Foxp3- T cells, which has attracted much interest as an approach toward cell-based therapy in clinical settings of undesired immune responses...
2018: Frontiers in Immunology
Harshavardhan Janga, Marina Aznaourova, Fabian Boldt, Katrin Damm, Arnold Grünweller, Leon N Schulte
CRISPR/Cas9-based approaches have greatly facilitated targeted genomic deletions. Contrary to coding genes however, which can be functionally knocked out by frame-shift mutagenesis, non-coding RNA (ncRNA) gene knockouts have remained challenging. Here we present a universal ncRNA knockout approach guided by epigenetic hallmarks, which enables robust gene silencing even in provisionally annotated gene loci. We build on previous work reporting the presence of overlapping histone H3 lysine 4 tri-methylation (H3K4me3) and DNaseI hypersensitivity sites around the transcriptional start sites of most genes...
2018: PloS One
Sheraz Khan, Mazhar Iqbal, Muhammad Tariq, Shahid M Baig, Wasim Abbas
HIV-1 latency allows the virus to persist until reactivation, in a transcriptionally silent form in its cellular reservoirs despite the presence of effective cART. Such viral persistence represents a major barrier to HIV eradication since treatment interruption leads to rebound plasma viremia. Polycomb group (PcG) proteins have recently got a considerable attention in regulating HIV-1 post-integration latency as they are involved in the repression of proviral gene expression through the methylation of histones...
2018: Clinical Epigenetics
Laura de Boni, Gilles Gasparoni, Carolin Haubenreich, Sascha Tierling, Ina Schmitt, Michael Peitz, Philipp Koch, Jörn Walter, Ullrich Wüllner, Oliver Brüstle
Background: Genetic predisposition and epigenetic alterations are both considered to contribute to sporadic neurodegenerative diseases (NDDs) such as Parkinson's disease (PD). Since cell reprogramming and the generation of induced pluripotent stem cells (iPSCs) are themselves associated with major epigenetic remodeling, it remains unclear to what extent iPSC-derived neurons lend themselves to model epigenetic disease-associated changes. A key question to be addressed in this context is whether iPSC-derived neurons exhibit epigenetic signatures typically observed in neurons derived from non-reprogrammed human embryonic stem cells (hESCs)...
2018: Clinical Epigenetics
Satyanarayan Rao, Tsu-Pei Chiu, Judith F Kribelbauer, Richard S Mann, Harmen J Bussemaker, Remo Rohs
BACKGROUND: DNA shape analysis has demonstrated the potential to reveal structure-based mechanisms of protein-DNA binding. However, information about the influence of chemical modification of DNA is limited. Cytosine methylation, the most frequent modification, represents the addition of a methyl group at the major groove edge of the cytosine base. In mammalian genomes, cytosine methylation most frequently occurs at CpG dinucleotides. In addition to changing the chemical signature of C/G base pairs, cytosine methylation can affect DNA structure...
February 6, 2018: Epigenetics & Chromatin
Francesca Giannese, Alessandra Luchetti, Giulia Barbiera, Valentina Lampis, Claudio Zanettini, Gun Peggy Knudsen, Simona Scaini, Dejan Lazarevic, Davide Cittaro, Francesca R D'Amato, Marco Battaglia
Respiratory and emotional responses to blood-acidifying inhalation of CO2 are markers of some human anxiety disorders, and can be enhanced by repeatedly cross-fostering (RCF) mouse pups from their biological mother to unrelated lactating females. Yet, these dynamics remain poorly understood. We show RCF-associated intergenerational transmission of CO2 sensitivity in normally-reared mice descending from RCF-exposed females, and describe the accompanying alterations in brain DNA methylation patterns. These epigenetic signatures were compared to DNA methylation profiles of monozygotic twins discordant for emotional reactivity to a CO2 challenge...
February 2, 2018: Scientific Reports
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