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https://www.readbyqxmd.com/read/28319142/microrna-32-promotes-calcification-in-vascular-smooth-muscle-cells-implications-as-a-novel-marker-for-coronary-artery-calcification
#1
Jianghua Liu, Xinhua Xiao, Yingying Shen, Ling Chen, Canxin Xu, Heng Zhao, Ying Wu, Qinghai Zhang, Jing Zhong, Zhenwang Tang, Changhui Liu, Qiang Zhao, Yi Zheng, Renxian Cao, Xuyu Zu
Cardiovascular calcification is one of the most severe outcomes associated with cardiovascular disease and often results in significant morbidity and mortality. Previous reports indicated that epigenomic regulation of microRNAs (miRNAs) might play important roles in vascular smooth muscle cell (VSMC) calcification. Here, we identified potential key miRNAs involved in vascular calcification in vivo and investigated the role of miR-32-5p (miR-32). According to microarray analysis, we observed increased expression of miR-125b, miR-30a, and miR-32 and decreased expression of miR-29a, miR-210, and miR-320 during the progression of vascularcalcification...
2017: PloS One
https://www.readbyqxmd.com/read/28315703/molecular-endocrinology-of-vitamin-d-on-the-epigenome-level
#2
REVIEW
Carsten Carlberg
The molecular endocrinology of vitamin D is based on the facts that i) its metabolite 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) is the high affinity ligand of the nuclear receptor vitamin D receptor (VDR) and ii) the transcription factor VDR is the unique target of 1,25(OH)2D3 in the nucleus. Short-term alterations of the epigenome are primarily changes in the post-translational modification status of nucleosome-forming histone proteins, the consequences of which are i) a local increase or decrease in chromatin accessibility and ii) the activation or repression of gene transcription...
March 15, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28315368/the-emerging-role-of-pi3k-akt-mediated-epigenetic-regulation-in-cancer
#3
REVIEW
Jennifer M Spangle, Thomas M Roberts, Jean J Zhao
The PI3-kinase/AKT pathway integrates signals from external cellular stimuli to regulate essential cellular functions, and is frequently aberrantly activated in human cancers. Recent research demonstrates that tight regulation of the epigenome is critical in preserving and restricting transcriptional activation, which can impact cellular growth and proliferation. In this review we examine mechanisms by which the PI3K/AKT pathway regulates the epigenome to promote oncogenesis, and highlight how connections between PI3K/AKT and the epigenome may impact the future therapeutic treatment of cancers featuring a hyperactivated PI3K/AKT pathway...
March 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28314379/rejuvenation-by-partial-reprogramming-of-the-epigenome
#4
Andrew R Mendelsohn, James Larrick, Jennifer L Lei
Epigenetic variation with age is one of the most important hallmarks of aging. Resetting or repairing the epigenome of aging cells in intact animals may rejuvenate the cells and perhaps the entire organism. In fact, differentiated adult cells, which by definition have undergone some epigenetic changes, are capable of being rejuvenated and reprogrammed to create pluripotent stem cells and viable cloned animals. Apparently, such reprogramming is capable of completely resetting the epigenome. However, attempts to fully reprogram differentiated cells in adult animals have failed in part because reprogramming leads to formation of teratomas...
March 17, 2017: Rejuvenation Research
https://www.readbyqxmd.com/read/28303888/dna-methylation-signatures-in-peripheral-blood-strongly-predict-all-cause-mortality
#5
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/28302822/the-cancer-epigenome-concepts-challenges-and-therapeutic-opportunities
#6
REVIEW
Mark A Dawson
Cancer biology is profoundly influenced by changes in the epigenome. Because the dynamic plasticity of the epigenome lends itself well to therapeutic manipulation, the past few years have witnessed an unprecedented investment in the development, characterization, and translation of targeted epigenetic therapies. In this review, I provide a broad context for recent developments that offer a greater understanding of how epigenetic regulators facilitate the initiation, maintenance, and evolution of cancer. I discuss newly developed epigenetic therapies and the cellular and molecular mechanisms that may govern sensitivity and resistance to these agents...
March 17, 2017: Science
https://www.readbyqxmd.com/read/28302717/regulatory-signatures-of-liver-regeneration-distilled-by-integrative-analysis-of-mrna-histone-methylation-and-proteomics
#7
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
#8
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/28302177/cepip-context-dependent-epigenomic-weighting-for-prioritization-of-regulatory-variants-and-disease-associated-genes
#9
Mulin Jun Li, Miaoxin Li, Zipeng Liu, Bin Yan, Zhicheng Pan, Dandan Huang, Qian Liang, Dingge Ying, Feng Xu, Hongcheng Yao, Panwen Wang, Jean-Pierre A Kocher, Zhengyuan Xia, Pak Chung Sham, Jun S Liu, Junwen Wang
It remains challenging to predict regulatory variants in particular tissues or cell types due to highly context-specific gene regulation. By connecting large-scale epigenomic profiles to expression quantitative trait loci (eQTLs) in a wide range of human tissues/cell types, we identify critical chromatin features that predict variant regulatory potential. We present cepip, a joint likelihood framework, for estimating a variant's regulatory probability in a context-dependent manner. Our method exhibits significant GWAS signal enrichment and is superior to existing cell type-specific methods...
March 16, 2017: Genome Biology
https://www.readbyqxmd.com/read/28301317/challenges-in-the-analysis-of-epigenetic-biomarkers-in-clinical-samples
#10
José Luis García-Giménez, Salvador Mena-Mollá, Jesús Beltrán-García, Fabian Sanchis-Gomar
Epigenetic modifications represent an interesting landscape which can describe relevant features of human disease. Epigenetic biomarkers show several advantages as disease biomarkers because they provide information about gene function, specific endophenotypes and can even incorporate information from the environment and the natural history of disease. The improvement in genomic and epigenomic technologies has revolutionized the current comprehension of biological processes underlying health and disease. However, now is the time to adopt these new technologies to improve human health, thus converting this information into reliable biomarkers...
March 16, 2017: Clinical Chemistry and Laboratory Medicine: CCLM
https://www.readbyqxmd.com/read/28301256/sperm-epigenetics-in-the-study-of-male-fertility-offspring-health-and-potential-clinical-applications
#11
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/28298479/cyst-nematode-parasitism-induces-dynamic-changes-in-the-root-epigenome
#12
Tarek Hewezi, Thomas Lane, Sarbottam Piya, Aditi Rambani, J Hollis Rice, Meg Staton
A growing body of evidence indicates that epigenetic modifications can provide efficient, dynamic, and reversible cellular responses to a wide range of environmental stimuli. However, the significance of epigenetic modifications in plant-pathogen interactions remains largely unexplored. In this study, we provide a comprehensive analysis of epigenome changes during the compatible interaction between the beet cyst nematode Heterodera schachtii and Arabidopsis (Arabidopsis thaliana). Whole genome bisulfite sequencing was conducted to assess the dynamic changes in the methylome of Arabidopsis roots in response to H schachtii infection...
March 15, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28294608/an-engineered-split-tet2-enzyme-for-inducible-epigenetic-remodeling
#13
Minjung Lee, Jia Li, Yi Liang, Guolin Ma, Jixiang Zhang, Lian He, Yuliang Liu, Qian Li, Minyong Li, Deqiang Sun, Yubin Zhou, Yun Huang
The Ten-eleven translocation (TET) family of 5-methylcytosine (5mC) dioxygenases catalyze the conversion of 5mC into 5-hydroxymethylcytosine (5hmC) and further oxidized species to promote active DNA demethylation. Here we engineered a split-TET2 enzyme to enable temporal control of 5mC oxidation and subsequent remodeling of epigenetic states in mammalian cells. We further demonstrate the use of this chemically-inducible system to dissect the correlation between DNA hydroxymethylation and chromatin accessibility in the mammalian genome...
March 15, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28292958/molecular-mechanisms-and-therapeutic-targets-in-pediatric-brain-tumors
#14
REVIEW
Kun-Wei Liu, Kristian W Pajtler, Barbara C Worst, Stefan M Pfister, Robert J Wechsler-Reya
Brain tumors are among the leading causes of cancer-related deaths in children. Although surgery, aggressive radiation, and chemotherapy have improved outcomes, many patients still die of their disease. Moreover, those who survive often suffer devastating long-term side effects from the therapies. A greater understanding of the molecular underpinnings of these diseases will drive the development of new therapeutic approaches. Advances in genomics and epigenomics have provided unprecedented insight into the molecular diversity of these diseases and, in several cases, have revealed key genes and signaling pathways that drive tumor growth...
March 14, 2017: Science Signaling
https://www.readbyqxmd.com/read/28292439/integrated-molecular-characterization-of-uterine-carcinosarcoma
#15
Andrew D Cherniack, Hui Shen, Vonn Walter, Chip Stewart, Bradley A Murray, Reanne Bowlby, Xin Hu, Shiyun Ling, Robert A Soslow, Russell R Broaddus, Rosemary E Zuna, Gordon Robertson, Peter W Laird, Raju Kucherlapati, Gordon B Mills, John N Weinstein, Jiashan Zhang, Rehan Akbani, Douglas A Levine
We performed genomic, epigenomic, transcriptomic, and proteomic characterizations of uterine carcinosarcomas (UCSs). Cohort samples had extensive copy-number alterations and highly recurrent somatic mutations. Frequent mutations were found in TP53, PTEN, PIK3CA, PPP2R1A, FBXW7, and KRAS, similar to endometrioid and serous uterine carcinomas. Transcriptome sequencing identified a strong epithelial-to-mesenchymal transition (EMT) gene signature in a subset of cases that was attributable to epigenetic alterations at microRNA promoters...
March 13, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28289683/multidimensional-integrative-genomics-approaches-to-dissecting-cardiovascular-disease
#16
REVIEW
Douglas Arneson, Le Shu, Brandon Tsai, Rio Barrere-Cain, Christine Sun, Xia Yang
Elucidating the mechanisms of complex diseases such as cardiovascular disease (CVD) remains a significant challenge due to multidimensional alterations at molecular, cellular, tissue, and organ levels. To better understand CVD and offer insights into the underlying mechanisms and potential therapeutic strategies, data from multiple omics types (genomics, epigenomics, transcriptomics, metabolomics, proteomics, microbiomics) from both humans and model organisms have become available. However, individual omics data types capture only a fraction of the molecular mechanisms...
2017: Frontiers in Cardiovascular Medicine
https://www.readbyqxmd.com/read/28289476/dna-methylation-at-modifier-genes-of-lung-disease-severity-is-altered-in-cystic-fibrosis
#17
Milena Magalhães, Isabelle Rivals, Mireille Claustres, Jessica Varilh, Mélodie Thomasset, Anne Bergougnoux, Laurent Mely, Sylvie Leroy, Harriet Corvol, Loïc Guillot, Marlène Murris, Emmanuelle Beyne, Davide Caimmi, Isabelle Vachier, Raphaël Chiron, Albertina De Sario
BACKGROUND: Lung disease progression is variable among cystic fibrosis (CF) patients and depends on DNA mutations in the CFTR gene, polymorphic variations in disease modifier genes, and environmental exposure. The contribution of genetic factors has been extensively investigated, whereas the mechanism whereby environmental factors modulate the lung disease is unknown. In this project, we hypothesized that (i) reiterative stress alters the epigenome in CF-affected tissues and (ii) DNA methylation variations at disease modifier genes modulate the lung function in CF patients...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28289275/epigenetic-programming-by-stress-and-glucocorticoids-along-the-human-lifespan
#18
A S Zannas, G P Chrousos
Psychosocial stress triggers a set of behavioral, neural, hormonal, and molecular responses that can be a driving force for survival when adaptive and time-limited, but may also contribute to a host of disease states if dysregulated or chronic. The beneficial or detrimental effects of stress are largely mediated by the hypothalamic-pituitary axis, a highly conserved neurohormonal cascade that culminates in systemic secretion of glucocorticoids. Glucocorticoids activate the glucocorticoid receptor, a ubiquitous nuclear receptor that not only causes widespread changes in transcriptional programs, but also induces lasting epigenetic modifications in many target tissues...
March 14, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28289216/b-vitamins-attenuate-the-epigenetic-effects-of-ambient-fine-particles-in-a-pilot-human-intervention-trial
#19
Jia Zhong, Oskar Karlsson, Guan Wang, Jun Li, Yichen Guo, Xinyi Lin, Michele Zemplenyi, Marco Sanchez-Guerra, Letizia Trevisi, Bruce Urch, Mary Speck, Liming Liang, Brent A Coull, Petros Koutrakis, Frances Silverman, Diane R Gold, Tangchun Wu, Andrea A Baccarelli
Acute exposure to fine particle (PM2.5) induces DNA methylation changes implicated in inflammation and oxidative stress. We conducted a crossover trial to determine whether B-vitamin supplementation averts such changes. Ten healthy adults blindly received a 2-h, controlled-exposure experiment to sham under placebo, PM2.5 (250 μg/m(3)) under placebo, and PM2.5 (250 μg/m(3)) under B-vitamin supplementation (2.5 mg/d folic acid, 50 mg/d vitamin B6, and 1 mg/d vitamin B12), respectively. We profiled epigenome-wide methylation before and after each experiment using the Infinium HumanMethylation450 BeadChip in peripheral CD4(+) T-helper cells...
March 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28288101/opposing-macrophage-polarization-programs-show-extensive-epigenomic-and-transcriptional-cross-talk
#20
Viviana Piccolo, Alessia Curina, Marco Genua, Serena Ghisletti, Marta Simonatto, Arianna Sabò, Bruno Amati, Renato Ostuni, Gioacchino Natoli
Stimulation of macrophages with interferon-γ (IFN-γ) and interleukin 4 (IL-4) triggers distinct and opposing activation programs. During mixed infections or cancer, macrophages are often exposed to both cytokines, but how these two programs influence each other remains unclear. We found that IFN-γ and IL-4 mutually inhibited the epigenomic and transcriptional changes induced by each cytokine alone. Computational and functional analyses revealed the genomic bases for gene-specific cross-repression. For instance, while binding motifs for the transcription factors STAT1 and IRF1 were associated with robust and IL-4-resistant responses to IFN-γ, their coexistence with binding sites for auxiliary transcription factors such as AP-1 generated vulnerability to IL-4-mediated inhibition...
March 13, 2017: Nature Immunology
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