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Epigenetic methylation signature

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https://www.readbyqxmd.com/read/28334816/dynamic-changes-in-chromatin-states-during-specification-and-differentiation-of-adult-intestinal-stem-cells
#1
Juri Kazakevych, Sergi Sayols, Berith Messner, Christina Krienke, Natalia Soshnikova
Epigenetic mechanisms, including chromatin structure, chromatin dynamics and histone modifications play an important role for maintenance and differentiation of pluripotent embryonic stem cells. However, little is known about the molecular mechanisms of adult stem cell specification and differentiation. Here, we used intestinal stem cells (ISCs) as a model system to reveal the epigenetic changes coordinating gene expression programs during these processes. We found that two distinct epigenetic mechanisms participate in establishing the transcriptional program promoting ISC specification from embryonic progenitors...
March 7, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334074/genome-wide-analysis-reveals-that-exon-methylation-facilitates-its-selective-usage-in-the-human-transcriptome
#2
Shengli Li, Jiwei Zhang, Shenglin Huang, Xianghuo He
DNA methylation, especially in promoter regions, is a well-characterized epigenetic marker related to gene expression regulation in eukaryotes. However, the role of intragenic DNA methylation in the usage of corresponding exons still remains elusive. In this study, we described the DNA methylome across 10 human tissues. The human genome showed both conserved and varied methylation levels among these tissues. We found that the methylation densities in promoters and first exons were negatively correlated with the corresponding gene expression level...
February 16, 2017: Briefings in Bioinformatics
https://www.readbyqxmd.com/read/28332497/epigenetically-driven-anatomical-diversity-of-synovial-fibroblasts-guides-joint-specific-fibroblast-functions
#3
Mojca Frank-Bertoncelj, Michelle Trenkmann, Kerstin Klein, Emmanuel Karouzakis, Hubert Rehrauer, Anna Bratus, Christoph Kolling, Maria Armaka, Andrew Filer, Beat A Michel, Renate E Gay, Christopher D Buckley, George Kollias, Steffen Gay, Caroline Ospelt
A number of human diseases, such as arthritis and atherosclerosis, include characteristic pathology in specific anatomical locations. Here we show transcriptomic differences in synovial fibroblasts from different joint locations and that HOX gene signatures reflect the joint-specific origins of mouse and human synovial fibroblasts and synovial tissues. Alongside DNA methylation and histone modifications, bromodomain and extra-terminal reader proteins regulate joint-specific HOX gene expression. Anatomical transcriptional diversity translates into joint-specific synovial fibroblast phenotypes with distinct adhesive, proliferative, chemotactic and matrix-degrading characteristics and differential responsiveness to TNF, creating a unique microenvironment in each joint...
March 23, 2017: Nature Communications
https://www.readbyqxmd.com/read/28328977/jmjd3-aids-in-reprogramming-of-bone-marrow-progenitor-cells-to-hepatic-phenotype-through-epigenetic-activation-of-hepatic-transcription-factors
#4
Veena Kochat, Zaffar Equbal, Prakash Baligar, Vikash Kumar, Madhulika Srivastava, Asok Mukhopadhyay
The strictly regulated unidirectional differentiation program in some somatic stem/progenitor cells has been found to be modified in the ectopic site (tissue) undergoing regeneration. In these cases, the lineage barrier is crossed by either heterotypic cell fusion or direct differentiation. Though studies have shown the role of coordinated genetic and epigenetic mechanisms in cellular development and differentiation, how the lineage fate of adult bone marrow progenitor cells (BMPCs) is reprogrammed during liver regeneration and whether this lineage switch is stably maintained are not clearly understood...
2017: PloS One
https://www.readbyqxmd.com/read/28324041/line1-cpg-dna-hypomethylation-in-granulosa-cells-and-blood-leukocytes-is-associated-with-pcos-and-related-traits
#5
Pooja Sagvekar, Vijay Mangoli, Sadhana Desai, Anushree Patil, Srabani Mukherjee
CONTEXT: Altered global DNA methylation is indicative of epigenomic instability concerning chronic disease-states. Investigating its incidence and association with polycystic ovary syndrome (PCOS) is essential towards understanding the etiopathogenesis of this disorder. OBJECTIVES: To assess, global DNA methylation differences in peripheral blood leukocytes (PBLs) and cumulus granulosa cells (CGCs) of PCOS and controls and their association with PCOS and its traits...
January 9, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28320934/allele-specific-non-cg-dna-methylation-marks-domains-of-active-chromatin-in-female-mouse-brain
#6
Christopher L Keown, Joel B Berletch, Rosa Castanon, Joseph R Nery, Christine M Disteche, Joseph R Ecker, Eran A Mukamel
DNA methylation at gene promoters in a CG context is associated with transcriptional repression, including at genes silenced on the inactive X chromosome in females. Non-CG methylation (mCH) is a distinct feature of the neuronal epigenome that is differentially distributed between males and females on the X chromosome. However, little is known about differences in mCH on the active (Xa) and inactive (Xi) X chromosomes because stochastic X-chromosome inactivation (XCI) confounds allele-specific epigenomic profiling...
March 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28303888/dna-methylation-signatures-in-peripheral-blood-strongly-predict-all-cause-mortality
#7
Yan Zhang, Rory Wilson, Jonathan Heiss, Lutz P Breitling, Kai-Uwe Saum, Ben Schöttker, Bernd Holleczek, Melanie Waldenberger, Annette Peters, Hermann Brenner
DNA methylation (DNAm) has been revealed to play a role in various diseases. Here we performed epigenome-wide screening and validation to identify mortality-related DNAm signatures in a general population-based cohort with up to 14 years follow-up. In the discovery panel in a case-cohort approach, 11,063 CpGs reach genome-wide significance (FDR<0.05). 58 CpGs, mapping to 38 well-known disease-related genes and 14 intergenic regions, are confirmed in a validation panel. A mortality risk score based on ten selected CpGs exhibits strong association with all-cause mortality, showing hazard ratios (95% CI) of 2...
March 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28302717/regulatory-signatures-of-liver-regeneration-distilled-by-integrative-analysis-of-mrna-histone-methylation-and-proteomics
#8
Yoshihiro Sato, Yasutake Katoh, Mitsuyo Matsumoto, Masaki Sato, Masayuki Ebina, Ari Itoh-Nakadai, Ryo Funayama, Keiko Nakayama, Michiaki Unno, Kazuhiko Igarashi
The capacity of the liver to regenerate is likely to be encoded as a plasticity of molecular networks within the liver. By applying a combination of comprehensive analyses of the epigenome, transcriptome and proteome, we herein depict the molecular landscape of liver regeneration. We demonstrated that histone H3K4 was tri-methylated at the promoter regions of many loci, among which only a fraction including cell-cycle-related genes were transcriptionally up-regulated. A cistrome analysis guided by the histone methylation patterns and the transcriptome identified FOXM1 as the key transcription factor promoting liver regeneration, which was confirmed in vitro using a hepatocarcinoma cell line...
March 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28302680/genomic-and-epigenomic-heterogeneity-of-hepatocellular-carcinoma
#9
De-Chen Lin, Anand Mayakonda, Huy Q Dinh, Pinbo Huang, Lehang Lin, Xiaoping Liu, Ling-Wen Ding, Jie Wang, Benjamin Berman, Erwei Song, Dong Yin, H Phillip Koeffler
Understanding the intratumoral heterogeneity of hepatocellular carcinoma (HCC) is instructive for developing personalized therapy and identifying molecular biomarkers. Here we applied whole-exome sequencing to 69 samples from 11 patients to resolve the genetic architecture of subclonal diversification. Spatial genomic diversity was found in all 11 HCC cases, with 29% of driver mutations being heterogeneous, including TERT, ARID1A, NOTCH2, and STAG2. Similar with other cancer types, TP53 mutations were always shared between all tumor regions i...
February 20, 2017: Cancer Research
https://www.readbyqxmd.com/read/28301256/sperm-epigenetics-in-the-study-of-male-fertility-offspring-health-and-potential-clinical-applications
#10
Timothy G Jenkins, Kenneth I Aston, Emma R James, Douglas T Carrell
The mammalian sperm contains a highly unique and specialized epigenetic landscape that offers a great degree of interesting research opportunities. One key discriminating feature of the mature sperm epigenome is that it, in theory, represents both remnant marks used throughout spermatogenesis to generate sperm cells competent to perform their function, but also marks that appear to be useful beyond fertilization. Key questions must be asked about the utility of these marks and the multiple purposes that may be served...
April 2017: Systems Biology in Reproductive Medicine
https://www.readbyqxmd.com/read/28298930/predicting-the-remaining-lifespan-and-cultivation-related-loss-of-osteogenic-capacity-of-bone-marrow-multipotential-stromal-cells-applicable-across-a-broad-donor-age-range
#11
Sarah M Churchman, Sally A Boxall, Dennis McGonagle, Elena A Jones
Background and Objectives. Culture expanded multipotential stromal cells (MSCs) have considerable potential for bone regeneration therapy but their wider use is constrained by the lack of simple and predictive assays of functional potency. Extended passaging leads to loss of multipotency but speed of decline depends on MSC donor age. The aim of this study was to develop an assay predictive of MSC culture longevity applicable to a broad donor age range. Materials and Methods. Bone marrow (BM, n = 7) was obtained from a diverse range (2-72 years) of healthy donors...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28293299/identification-of-epigenetic-signature-associated-with-alpha-thalassemia-mental-retardation-x-linked-syndrome
#12
Laila C Schenkel, Kristin D Kernohan, Arran McBride, Ditta Reina, Amanda Hodge, Peter J Ainsworth, David I Rodenhiser, Guillaume Pare, Nathalie G Bérubé, Cindy Skinner, Kym M Boycott, Charles Schwartz, Bekim Sadikovic
BACKGROUND: Alpha thalassemia/mental retardation X-linked syndrome (ATR-X) is caused by a mutation at the chromatin regulator gene ATRX. The mechanisms involved in the ATR-X pathology are not completely understood, but may involve epigenetic modifications. ATRX has been linked to the regulation of histone H3 and DNA methylation, while mutations in the ATRX gene may lead to the downstream epigenetic and transcriptional effects. Elucidating the underlying epigenetic mechanisms altered in ATR-X will provide a better understanding about the pathobiology of this disease, as well as provide novel diagnostic biomarkers...
2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28289824/a-mirna-signature-for-an-environmental-heterocyclic-amine-defined-by-a-multi-organ-carcinogenicity-bioassay-in-the-rat
#13
Ying-Shiuan Chen, Rong Wang, Wan-Mohaiza Dashwood, Christiane V Löhr, David E Williams, Emily Ho, Susanne Mertens-Talcott, Roderick H Dashwood
Heterocyclic amines (HCAs) produced during high-temperature cooking have been studied extensively in terms of their genotoxic/genetic effects, but recent work has implicated epigenetic mechanisms involving non-coding RNAs. Colon tumors induced in the rat by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) have altered microRNA (miRNA) signatures linked to dysregulated pluripotency factors, such as c-Myc and Krüppel-like factor 4 (KLF4). We tested the hypothesis that dysregulated miRNAs from PhIP-induced colon tumors would provide a "PhIP signature" for use in other target organs obtained from a 1-year carcinogenicity bioassay in the rat...
March 13, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28278225/identification-of-endometrial-cancer-methylation-features-using-combined-methylation-analysis-methods
#14
Michael P Trimarchi, Pearlly Yan, Joanna Groden, Ralf Bundschuh, Paul J Goodfellow
BACKGROUND: DNA methylation is a stable epigenetic mark that is frequently altered in tumors. DNA methylation features are attractive biomarkers for disease states given the stability of DNA methylation in living cells and in biologic specimens typically available for analysis. Widespread accumulation of methylation in regulatory elements in some cancers (specifically the CpG island methylator phenotype, CIMP) can play an important role in tumorigenesis. High resolution assessment of CIMP for the entire genome, however, remains cost prohibitive and requires quantities of DNA not available for many tissue samples of interest...
2017: PloS One
https://www.readbyqxmd.com/read/28273634/dynamic-changes-of-epigenetic-signatures-during-chondrogenic-and-adipogenic-differentiation-of-mesenchymal-stem-cells
#15
REVIEW
Navid Saidi, Majdedin Ghalavand, Mohammad Sadegh Hashemzadeh, Ruhollah Dorostkar, Hamed Mohammadi, Ahmad Mahdian-Shakib
Extensive studies have been performed to clarify the processes during which mesenchymal stem cells (MSCs) differentiate into their lineage fates. In vitro differentiation of MSCs into distinct lineages have attracted the focus of a large number of clinical investigations. Although the gene expression profiling during differentiation of MSC toward bone, cartilage, and adipocytes is well established, the master regulators by which MSC fate can be controlled are not entirely determined. During differentiation of MSCs into a special cell fate, epigenetic mechanisms considered as the primary mediators that suppress the irrelevant genes and activate the genes required for a specific cell lineage...
March 5, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28250848/tissue-specific-methylation-profile-in-obese-patients-with-type-2-diabetes-before-and-after-roux-en-y-gastric-bypass
#16
REVIEW
Priscila Sala, Raquel Susana Matos de Miranda Torrinhas, Danielle Cristina Fonseca, Graziela Rosa Ravacci, Dan Linetzky Waitzberg, Daniel Giannella-Neto
Eating habits, lifestyles, and exposure to specific environmental factors can greatly impact the risk of developing type 2 diabetes (T2D), influence the genome epigenetically, and affect the expression of genes, including genes related to glycemic control, at any stage of life. The epigenetic mechanism underlying obesity and T2D pathogenesis remains poorly understood. Conventional strategies for the treatment of obesity and its comorbidities often have poor long-term adherence, and pharmacological interventions are limited...
2017: Diabetology & Metabolic Syndrome
https://www.readbyqxmd.com/read/28228863/medulloblastoma-and-ependymoma-cells-display-increased-levels-of-5-carboxylcytosine-and-elevated-tet1-expression
#17
Ashley Ramsawhook, Lara Lewis, Beth Coyle, Alexey Ruzov
BACKGROUND: Alteration of DNA methylation (5-methylcytosine, 5mC) patterns represents one of the causes of tumorigenesis and cancer progression. Tet proteins can oxidise 5mC to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine and 5-carboxylcytosine (5caC). Although the roles of these oxidised forms of 5mC (oxi-mCs) in cancer pathogenesis are still largely unknown, there are indications that they may be involved in the mechanisms of malignant transformation. Thus, reduction of 5hmC content represents an epigenetic hallmark of human tumours, and according to our recent report, 5caC is enriched in a proportion of breast cancers and gliomas...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28223506/intragenic-cpg-islands-play-important-roles-in-bivalent-chromatin-assembly-of-developmental-genes
#18
Sun-Min Lee, Jungwoo Lee, Kyung-Min Noh, Won-Young Choi, Sejin Jeon, Goo Taeg Oh, Jeongsil Kim-Ha, Yoonhee Jin, Seung-Woo Cho, Young-Joon Kim
CpG, 5'-C-phosphate-G-3', islands (CGIs) have long been known for their association with enhancers, silencers, and promoters, and for their epigenetic signatures. They are maintained in embryonic stem cells (ESCs) in a poised but inactive state via the formation of bivalent chromatin containing both active and repressive marks. CGIs also occur within coding sequences, where their functional role has remained obscure. Intragenic CGIs (iCGIs) are largely absent from housekeeping genes, but they are found in all genes associated with organ development and cell lineage control...
March 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28211484/regulation-of-mrna-splicing-by-mecp2-via-epigenetic-modifications-in-the-brain
#19
Tian-Lin Cheng, Jingqi Chen, Huida Wan, Bin Tang, Weidong Tian, Lujian Liao, Zilong Qiu
Mutations of X-linked gene Methyl CpG binding protein 2 (MECP2) are the major causes of Rett syndrome (RTT), a severe neurodevelopmental disorder. Duplications of MECP2-containing genomic segments lead to severe autistic symptoms in human. MECP2-coding protein methyl-CpG-binding protein 2 (MeCP2) is involved in transcription regulation, microRNA processing and mRNA splicing. However, molecular mechanisms underlying the involvement of MeCP2 in mRNA splicing in neurons remain largely elusive. In this work we found that the majority of MeCP2-associated proteins are involved in mRNA splicing using mass spectrometry analysis with multiple samples from Mecp2-null rat brain, mouse primary neuron and human cell lines...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28205577/epigenetic-signatures-of-invasive-status-in-populations-of-marine-invertebrates
#20
Alba Ardura, Anastasija Zaiko, Paloma Morán, Serge Planes, Eva Garcia-Vazquez
Epigenetics, as a DNA signature that affects gene expression and enables rapid reaction of an organism to environmental changes, is likely involved in the process of biological invasions. DNA methylation is an epigenetic mechanism common to plants and animals for regulating gene expression. In this study we show, for the first time in any marine species, significant reduction of global methylation levels during the expansive phase of a pygmy mussel (Xenostrobus securis) recent invasion in Europe (two-year old), while in older introductions such epigenetic signature of invasion was progressively reduced...
February 16, 2017: Scientific Reports
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