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Epigenetics: Official Journal of the DNA Methylation Society

Jian V Huang, Andres Cardenas, Elena Colicino, C Mary Schooling, Sheryl L Rifas-Shiman, Golareh Agha, Yinan Zheng, Lifang Hou, Allan C Just, Augusto A Litonjua, Dawn L DeMeo, Xihong Lin, Emily Oken, Marie-France Hivert, Andrea A Baccarelli
Obesity is associated with higher cardio-metabolic risk even in childhood and adolescence; whether this association is mediated by epigenetic mechanisms remains unclear. We examined the extent to which mid-childhood body mass index (BMI) z-score (median age 7.7 years) was associated with cardio-metabolic risk score in early adolescence (median age 12.9 years) via mid-childhood DNA methylation among 265 children in the Project Viva. We measured DNA methylation in leukocytes using the Infinium Human Methylation450K BeadChip...
November 9, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Hannah R Parker, Stephany Orjuela, Andreia Martinho Oliveira, Fabrizio Cereatti, Matthias Sauter, Henriette Heinrich, Giulia Tanzi, Achim Weber, Paul Komminoth, Stephan Vavricka, Luca Albanese, Federico Buffoli, Mark D Robinson, Giancarlo Marra
Sessile serrated adenomas/polyps (SSA/Ps) are the putative precursors of the ~20% of colon cancers with the CpG island methylator phenotype (CIMP), but their molecular features are poorly understood. We used high-throughput analysis of DNA methylation and gene expression to investigate the epigenetic phenotype of SSA/Ps. Fresh-tissue samples of 17 SSA/Ps and (for comparison purposes) 15 conventional adenomas (cADNs)-each with a matched sample of normal mucosa-were prospectively collected during colonoscopy (total no...
November 6, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Adel Derghal, Mehdi Djelloul, Myriam Azzarelli, Sébastien Degonon, Franck Tourniaire, Jean-François Landrier, Lourdes Mounien
The central nervous system monitors modifications in metabolic parameters or hormone levels (leptin) and elicits adaptive responses such as food intake and glucose homeostasis regulation. Particularly, within the hypothalamus, pro-opiomelanocortin (POMC) neurons are crucial regulators of energy balance. Consistent with a pivotal role of the melanocortin system in the control of energy homeostasis, disruption of the Pomc gene causes hyperphagia and obesity. Pomc gene expression is tightly controlled by different mechanisms...
November 5, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Juan Jose Carmona, Richard T Barfield, Tommaso Panni, Jamaji C Nwanaji-Enwerem, Allan C Just, John N Hutchinson, Elena Colicino, Stefan Karrasch, Simone Wahl, Sonja Kunze, Nadereh Jafari, Yinan Zheng, Lifang Hou, Dawn L DeMeo, Augusto A Litonjua, Pantel S Vokonas, Annette Peters, Xihong Lin, Joel Schwartz, Holger Schulz, Andrea A Baccarelli
DNA methylation is an epigenetic regulator of gene transcription, which has been found to be both metastable and variable within human cohort studies. Currently, few studies have been done to identify metastable DNA methylation biomarkers associated with longitudinal lung function decline in humans. The identification of such biomarkers is important for screening vulnerable populations. We hypothesized that quantifiable blood-based DNA methylation alterations would serve as metastable biomarkers of lung function decline and aging, which may help to discover new pathways and/or mechanisms related to pulmonary pathogenesis...
October 21, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Ina Zaimi, Dong Pei, Devin C Koestler, Carmen J Marsit, Immaculata De Vivo, Shelley S Tworoger, Alexandra E Shields, Karl T Kelsey, Dominique S Michaud
Assessing DNA methylation profiles in human blood has become a major focus of epidemiologic inquiry. Understanding variability in CpG-specific DNA methylation over moderate periods of time is a critical first step in identifying CpG sites that are candidates for DNA methylation-based etiologic, diagnostic and prognostic predictors of pathogenesis. Using the Illumina MethylationEPIC [850K] BeadArray, DNA methylation was profiled in paired whole blood samples collected approximately 1 year apart from 35 healthy women enrolled in the Nurses Study II cohort...
October 21, 2018: Epigenetics: Official Journal of the DNA Methylation Society
L Fontana, M F Bedeschi, S Maitz, A Cereda, C Faré, S Motta, A Seresini, P D'Ursi, A Orro, V Pecile, M Calvello, A Selicorni, F Lalatta, D Milani, S M Sirchia, M Miozzo, S Tabano
The identification of multilocus imprinting disturbances (MLID) appears fundamental to uncover molecular pathways underlying imprinting disorders (IDs) and to complete clinical diagnosis of patients. However, MLID genetic associated mechanisms remain largely unknown. To characterize MLID in Beckwith-Wiedemann (BWS) and Silver-Russell (SRS) syndromes, we profiled by MassARRAY the methylation of 12 imprinted differentially methylated regions (iDMRs) in 21 BWS and 7 SRS patients with chromosome 11p15.5 epimutations...
October 21, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Anne K Bozack, Andres Cardenas, Quazi Quamruzzaman, Mahmuder Rahman, Golam Mostofa, David C Christiani, Molly L Kile
Prenatal arsenic exposure is associated with adverse birth outcomes and disease risk later in life, which could be mediated through epigenetic dysregulation. We evaluated the association between arsenic and gestational age (GA) that was mediated through DNA methylation (DNAm) using data from a Bangladeshi birth cohort. Arsenic exposure was measured in maternal drinking water at ≤16 weeks GA and maternal toenails collected ≤1 month postpartum. Cord blood DNAm was measured using Infinium HumanMethylation450 arrays (n = 44, discovery phase)...
October 11, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Aziz Khan, Anthony Mathelier, Xuegong Zhang
Super-enhancers and stretch enhancers represent classes of transcriptional enhancers that have been shown to control the expression of cell identity genes and carry disease- and trait-associated variants. Specifically, super-enhancers are clusters of enhancers defined based on the binding occupancy of master transcription factors, chromatin regulators, or chromatin marks, while stretch enhancers are large chromatin-defined regulatory regions of at least 3,000 base pairs. Several studies have characterized these regulatory regions in numerous cell types and tissues to decipher their functional importance...
October 11, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Lu Gao, Robert Urman, Joshua Millstein, Kimberly D Siegmund, Louis Dubeau, Carrie V Breton
AXL is one of the TAM (TYRO3, AXL and MERTK) receptor tyrosine kinases and may be involved in airway inflammation. Little is known about how epigenetic changes in AXL may affect lung development during adolescence. We investigated the association between AXL DNA methylation at birth and lung function growth from 10 to 18 years of age in 923 subjects from the Children's Health Study (CHS). DNA methylation from newborn bloodspots was measured at multiple CpG loci across the regulatory regions of AXL using Pyrosequencing...
October 2, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Dafni Anastasiadi, Marc Vandeputte, Núria Sánchez-Baizán, François Allal, Francesc Piferrer
The integration of genomic and environmental influences into methylation patterns to bring about a phenotype is of central interest in developmental epigenetics, but many details are still unclear. The sex ratios of the species used here, the European sea bass, are determined by genetic and temperature influences. We created four families from parents known to produce offspring with different sex ratios, exposed larvae to masculinizing temperatures and examined, in juvenile gonads, the DNA methylation of seven genes related to sexual development by a targeted sequencing approach...
September 28, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Yunzhang Wang, Robert Karlsson, Erik Lampa, Qian Zhang, Åsa K Hedman, Malin Almgren, Catarina Almqvist, Allan F McRae, Riccardo E Marioni, Erik Ingelsson, Peter M Visscher, Ian J Deary, Lars Lind, Tiffany Morris, Stephan Beck, Nancy L Pedersen, Sara Hägg
Age-related changes in DNA methylation were observed in cross-sectional studies, but longitudinal evidence is still limited. Here, we aimed to characterize longitudinal age-related methylation patterns using 1011 blood samples collected from 385 Swedish twins (age at entry: mean 69 and standard deviation 9.7, 73 monozygotic and 96 dizygotic pairs) up to five times (mean 2.6) over 20 years (mean 8.7). We identified 1316 age-associated methylation sites (P<1.3×10-7 ) using a longitudinal epigenome-wide association study design...
September 28, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Yunzhang Wang, Nancy L Pedersen, Sara Hägg
Interindividual variability of DNA methylation is a mechanism of the epigenetic drift in aging. Studies on cross-sectional data have discovered a change in methylation variability in association with age. However, thus far, no method explored DNA methylation variability in longitudinal data, which was the aim of this study. First, we performed a simulation study to explore methods for estimating methylation variability in longitudinal data. Second, an epigenome-wide association study (EWAS) on 1011 longitudinal samples (385 individuals followed up to 18 years) was performed to identify age-varying methylation sites using these methods...
September 25, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Kai Fu, Haruko Nakano, Marco Morselli, Tiffany Chen, Herman Pappoe, Atsushi Nakano, Matteo Pellegrini
Abstracts Stem cell-based cardiogenesis has become a powerful tool to enhance our understanding of cardiac development and test novel therapeutics for cardiovascular diseases. However, transcriptional and epigenetic regulation of multiple transitional stages from pluripotent cells to committed cardiomyocytes has not yet been fully characterized. To characterize how transcription factors, lincRNAs and DNA methylation change at temporal developmental stages, and identify potential novel regulators during cardiogenesis...
September 21, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Jing Xue, Raad Z Gharaibeh, Edward W Pietryk, Cory Brouwer, Lisa M Tarantino, William Valdar, Folami Y Ideraabdullah
Suboptimal environmental conditions during development can substantially alter the epigenome. Stable environmentally-induced changes to the germline epigenome, in particular, have important implications for the health of the next generation. We showed previously that developmental vitamin D depletion (DVD) resulted in loss of DNA methylation at several imprinted loci over two generations. Here, we assessed the impact of DVD on genome-wide methylation in mouse sperm in order to characterize the number, extent and distribution of methylation changes in response to DVD and to find genes that may be susceptible to this prevalent environmental perturbation...
September 21, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Xinyi Lin, Jane Yi Lin Tan, Ai Ling Teh, Ives Yubin Lim, Samantha J Liew, Julia L MacIsaac, Yap Seng Chong, Peter D Gluckman, Michael S Kobor, Clara Yujing Cheong, Neerja Karnani
Accounting for cellular heterogeneity is essential in neonatal epigenome-wide association studies (EWAS) performed on heterogeneous tissues, such as umbilical cord tissue (CT) or cord blood (CB). Using a reference-panel-based statistical approach, the cell type composition of heterogeneous tissues can be estimated by comparison of whole tissue DNA methylation profiles with cell type-specific DNA methylation signatures. Currently, there is no adequate DNA methylation reference panel for CT, and existing CB panels have been generated on lower coverage Infinium HumanMethylation450 arrays...
September 20, 2018: Epigenetics: Official Journal of the DNA Methylation Society
Min-Ae Song, Thomas Ernst, Maarit Tiirikainen, Jörg Tost, Lynne R Wilkens, Linda Chang, Laurence N Kolonel, Loïc Le Marchand, Unhee Lim
Excess body fat, especially intra-abdominal fat, is a leading risk factor for metabolic diseases. Differentially methylated regions (DMRs) of two imprinted genes, insulin-like growth factor 2 (IGF2) and H19, have been associated with obesity due to their important roles in regulating body composition, but have not been examined in relation to intra-abdominal fat depots. Total body fat from whole-body dual energy X-ray absorptiometry and visceral and liver fat contents from abdominal magnetic resonance imaging in 48 healthy women aged 60-65 years (of White or Japanese ancestry) were each regressed on circulating leukocyte DNA methylation levels of IGF2 (at DMR0, DMR2a, and DMR2b) and H19 (at CTCF3) as assessed by pyrosequencing, while adjusting for age and race/ethnicity...
2018: Epigenetics: Official Journal of the DNA Methylation Society
Andigoni Malousi, Alexandra-Zoi Andreou, Elisavet Georgiou, Georgios Tzimagiorgis, Leda Kovatsi, Sofia Kouidou
Horvath's epigenetic clock consists of 353 CpGs whose methylation levels can accurately predict the age of individuals. Using bioinformatics analysis, we investigated the conformation, energy characteristics and presence of tentative splice sites of the sequences surrounding the epigenetic clock CpGs, in relation to the median methylation changes in different ages, the presence of CpG islands and their position in genes. Common characteristics in the 100 nt sequences surrounding the epigenetic clock CpGs are G-quadruplexes and/or tentative splice site motifs...
2018: Epigenetics: Official Journal of the DNA Methylation Society
Jasmin Beygo, Claudia Mertel, Sabine Kaya, Gabriele Gillessen-Kaesbach, Thomas Eggermann, Bernhard Horsthemke, Karin Buiting
Temple syndrome (TS14) is a rare imprinting disorder caused by genetic and epigenetic alterations on chromosome 14q32. A subset of these patients shows an imprinting defect (ID) where the paternal allele harbors a maternal epigenotype thus silencing the paternally expressed genes and leading to an increased expression of the maternally expressed genes. We investigated the grandparental origin of the incorrectly imprinted chromosome 14 in a cohort of 13 TS14 ID patients and their families. In seven families grandmaternal and, in six families, grandpaternal inheritance was observed...
2018: Epigenetics: Official Journal of the DNA Methylation Society
Eric Nilsson, Rachel Klukovich, Ingrid Sadler-Riggleman, Daniel Beck, Yeming Xie, Wei Yan, Michael K Skinner
Two of the most prevalent ovarian diseases affecting women's fertility and health are Primary Ovarian Insufficiency (POI) and Polycystic Ovarian Syndrome (PCOS). Previous studies have shown that exposure to a number of environmental toxicants can promote the epigenetic transgenerational inheritance of ovarian disease. In the current study, transgenerational changes to the transcriptome and epigenome of ovarian granulosa cells are characterized in F3 generation rats after ancestral vinclozolin or DDT exposures...
2018: Epigenetics: Official Journal of the DNA Methylation Society
Oriana Lo Re, Julien Douet, Marcus Buschbeck, Caterina Fusilli, Valerio Pazienza, Concetta Panebianco, Carlo Castruccio Castracani, Tommaso Mazza, Giovanni Li Volti, Manlio Vinciguerra
Hepatocellular carcinomas (HCCs) contain a sub-population of cancer stem cells (CSCs) that are responsible for tumor relapse, metastasis, and chemoresistance. We recently showed that loss of macroH2A1, a variant of the histone H2A and an epigenetic regulator of stem-cell function, in HCC leads to CSC-like features such as resistance to chemotherapeutic agents and growth of large and relatively undifferentiated tumors in xenograft models. These HCC cells silenced for macroH2A1 also exhibited stem-like metabolic changes consistent with enhanced glycolysis...
2018: Epigenetics: Official Journal of the DNA Methylation Society
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