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https://www.readbyqxmd.com/read/29691590/enhancer-reprogramming-in-tumor-progression-a-new-route-towards-cancer-cell-plasticity
#1
REVIEW
Luca Fagnocchi, Vittoria Poli, Alessio Zippo
Cancer heterogeneity arises during tumor progression as a consequence of genetic insults, environmental cues, and reversible changes in the epigenetic state, favoring tumor cell plasticity. The role of enhancer reprogramming is emerging as a relevant field in cancer biology as it supports adaptation of cancer cells to those environmental changes encountered during tumor progression and metastasis seeding. In this review, we describe the cancer-related alterations that drive oncogenic enhancer activity, leading to dysregulated transcriptional programs...
April 24, 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29691407/long-ncrna-a-rod-activates-its-target-gene-dkk1-at-its-release-from-chromatin
#2
Evgenia Ntini, Annita Louloupi, Julia Liz, Jose M Muino, Annalisa Marsico, Ulf Andersson Vang Ørom
Long ncRNAs are often enriched in the nucleus and at chromatin, but whether their dissociation from chromatin is important for their role in transcription regulation is unclear. Here, we group long ncRNAs using epigenetic marks, expression and strength of chromosomal interactions; we find that long ncRNAs transcribed from loci engaged in strong long-range chromosomal interactions are less abundant at chromatin, suggesting the release from chromatin as a crucial functional aspect of long ncRNAs in transcription regulation of their target genes...
April 24, 2018: Nature Communications
https://www.readbyqxmd.com/read/29691401/methylated-dnmt1-and-e2f1-are-targeted-for-proteolysis-by-l3mbtl3-and-crl4-dcaf5-ubiquitin-ligase
#3
Feng Leng, Jiekai Yu, Chunxiao Zhang, Salvador Alejo, Nam Hoang, Hong Sun, Fei Lu, Hui Zhang
Many non-histone proteins are lysine methylated and a novel function of this modification is to trigger the proteolysis of methylated proteins. Here, we report that the methylated lysine 142 of DNMT1, a major DNA methyltransferase that preserves epigenetic inheritance of DNA methylation patterns during DNA replication, is demethylated by LSD1. A novel methyl-binding protein, L3MBTL3, binds the K142-methylated DNMT1 and recruits a novel CRL4DCAF5 ubiquitin ligase to degrade DNMT1. Both LSD1 and PHF20L1 act primarily in S phase to prevent DNMT1 degradation by L3MBTL3-CRL4DCAF5 ...
April 24, 2018: Nature Communications
https://www.readbyqxmd.com/read/29691395/epigenetic-landscape-influences-the-liver-cancer-genome-architecture
#4
Natsuko Hama, Yasushi Totoki, Fumihito Miura, Kenji Tatsuno, Mihoko Saito-Adachi, Hiromi Nakamura, Yasuhito Arai, Fumie Hosoda, Tomoko Urushidate, Shoko Ohashi, Wakako Mukai, Nobuyoshi Hiraoka, Hiroyuki Aburatani, Takashi Ito, Tatsuhiro Shibata
The accumulations of different types of genetic alterations such as nucleotide substitutions, structural rearrangements and viral genome integrations and epigenetic alterations contribute to carcinogenesis. Here, we report correlation between the occurrence of epigenetic features and genetic aberrations by whole-genome bisulfite, whole-genome shotgun, long-read, and virus capture sequencing of 373 liver cancers. Somatic substitutions and rearrangement breakpoints are enriched in tumor-specific hypo-methylated regions with inactive chromatin marks and actively transcribed highly methylated regions in the cancer genome...
April 24, 2018: Nature Communications
https://www.readbyqxmd.com/read/29691382/snord116-dependent-diurnal-rhythm-of-dna-methylation-in-mouse-cortex
#5
Rochelle L Coulson, Dag H Yasui, Keith W Dunaway, Benjamin I Laufer, Annie Vogel Ciernia, Yihui Zhu, Charles E Mordaunt, Theresa S Totah, Janine M LaSalle
Rhythmic oscillations of physiological processes depend on integrating the circadian clock and diurnal environment. DNA methylation is epigenetically responsive to daily rhythms, as a subset of CpG dinucleotides in brain exhibit diurnal rhythmic methylation. Here, we show a major genetic effect on rhythmic methylation in a mouse Snord116 deletion model of the imprinted disorder Prader-Willi syndrome (PWS). More than 23,000 diurnally rhythmic CpGs are identified in wild-type cortex, with nearly all lost or phase-shifted in PWS...
April 24, 2018: Nature Communications
https://www.readbyqxmd.com/read/29691341/epigenetic-regulation-of-tumor-suppressors-by-helicobacter-pylori-enhances-ebv-induced-proliferation-of-gastric-epithelial-cells
#6
Saurabh Pandey, Hem Chandra Jha, Sanket Kumar Shukla, Meghan K Shirley, Erle S Robertson
Helicobacter pylori and Epstein-Barr virus (EBV) are two well-known contributors to cancer and can establish lifelong persistent infection in the host. This leads to chronic inflammation, which also contributes to development of cancer. Association with H. pylori increases the risk of gastric carcinoma, and coexistence with EBV enhances proliferation of infected cells. Further, H. pylori -EBV coinfection causes chronic inflammation in pediatric patients. We have established an H. pylori -EBV coinfection model system using human gastric epithelial cells...
April 24, 2018: MBio
https://www.readbyqxmd.com/read/29691302/repressing-the-repressor-ezh2-mediates-macrophage-activation
#7
Annette E Neele, Menno P J de Winther
In this issue of JEM , Zhang et al. (https://doi.org/10.1084/jem.20171417) show that the suppressive epigenetic enzyme Ezh2 is an important regulator of macrophage activation. The absence of Ezh2 leads to reduced cytokine secretion and suppresses macrophage-dependent disease development. They identify the antiinflammatory factor Socs3 as an important target for Ezh2 and thus show that regulation of suppressive histone modifications controls macrophage activation in disease.
April 24, 2018: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29690914/klk10-exon-3-unmethylated-pcr-product-concentration-a-new-potential-early-diagnostic-marker-in-ovarian-cancer-a-pilot-study
#8
Mustafa A El Sherbini, Amal A Mansour, Maha M Sallam, Emtiaz A Shaban, Zeinab A Shehab ElDin, Amr H El-Shalakany
BACKGROUND: KLK10 exon 3 hypermethylation correlated to tumor-specific lack of KLK10 expression in cancer cell lines and primary tumors. In the present study we investigate the possible role of KLK10 exon 3 methylation in ovarian tumor diagnosis and prognosis. RESULTS: Qualitative methylation-specific PCR (MSP) results did not show statistically significant differences in patient group samples (normal and tumor) where all samples were positive only for the unmethylated-specific PCR except for two malignant samples that were either doubly positive (serous carcinoma) or doubly negative (Sertoli-Leydig cell tumor) for the two MSP tests...
April 24, 2018: Journal of Ovarian Research
https://www.readbyqxmd.com/read/29690855/maternal-phthalate-and-personal-care-products-exposure-alters-extracellular-placental-mirna-profile-in-twin-pregnancies
#9
Jia Zhong, Andrea A Baccarelli, Abdallah Mansur, Michal Adir, Ravit Nahum, Russ Hauser, Valentina Bollati, Catherine Racowsky, Ronit Machtinger
Prenatal exposure to endocrine-disrupting chemicals (EDCs) exerts both short- and long-term adverse effects on the developing fetus. However, the mechanisms underlying these effects have yet to be uncovered. Maternal-fetal signaling is mediated in part by signaling molecules (eg, microRNAs [miRNAs]) contained in extracellular vesicles (EVs) that are released by the placenta into the maternal circulation. We investigated whether maternal exposure to the EDCs phthalates and personal care products alters the miRNA profile of placental-derived EVs circulating in maternal blood...
January 1, 2018: Reproductive Sciences
https://www.readbyqxmd.com/read/29690695/-comparative-analysis-of-methylation-profiles-in-tissues-of-oral-leukoplakia-and-oral-squamous-cell-carcinoma
#10
J Fu, Y Su, Y Liu, X Y Zhang
Objective: To compare the methylation profiles in tissues of oral leukoplakia (OLK) and oral squamous cell carcinoma (OSCC) with healthy tissues of oral mucosa, in order to identify the role of DNA methylation played in tumorigenesis. Methods: DNA samples extracted from tissues of 4 healthy oral mucosa, 4 OSCC and 4 OLK collected from patients of the Department of Oral Medicine, Capital Medical University School of Stomatology were examined and compared using Methylation 450 Bead Chip. The genes associated with differentially methylated CpG sites were selected for gene ontology (GO) analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment...
April 9, 2018: Zhonghua Kou Qiang Yi Xue za Zhi, Zhonghua Kouqiang Yixue Zazhi, Chinese Journal of Stomatology
https://www.readbyqxmd.com/read/29690599/clinicopathological-characteristics-and-mutations-driving-development-of-early-lung-adenocarcinoma-tumor-initiation-and-progression
#11
REVIEW
Kentaro Inamura
Lung cancer is the leading cause of cancer-related deaths worldwide, with lung adenocarcinoma representing the most common lung cancer subtype. Among all lung adenocarcinomas, the most prevalent subset develops via tumorigenesis and progression from atypical adenomatous hyperplasia (AAH) to adenocarcinoma in situ (AIS), to minimally invasive adenocarcinoma (MIA), to overt invasive adenocarcinoma with a lepidic pattern. This stepwise development is supported by the clinicopathological and molecular characteristics of these tumors...
April 23, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29689378/in-utero-and-lactational-exposure-of-dehp-increases-the-susceptibility-of-prostate-carcinogenesis-in-male-offspring-through-psca-hypomethylation
#12
Bin Xia, Yong Wang, Xiu Wang, Jianhui Wu, Qi Song, Zuyue Sun, Yunhui Zhang
As an ubiquitous environmental endocrine disruptor, di(2-ethylhexyl) phthalate (DEHP) has been shown to interfere with the development of reproductive organs and induce pathological changes in prostate. Our previous finding showed that in utero and lactational (IUL) DEHP exposure could disrupt the balance of testosterone and estrogen and increase the susceptibility of prostate carcinogenesis. The purpose of this study is to investigate whether the early-life specific epigenetic modifications could mediate the effect of DEHP exposure on prostate carcinogenesis in rodents, for epigenetic modifications play important roles in regulating prostate carcinogenesis...
April 21, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29689276/withaferin-a-and-sulforaphane-regulate-breast-cancer-cell-cycle-progression-through-epigenetic-mechanisms
#13
Kendra J Royston, Bidisha Paul, Susan Nozell, Rajani Rajbhandari, Trygve O Tollefsbol
Little is known about the effects of combinatorial dietary compounds on the regulation of epigenetic mechanisms involved in breast cancer prevention. The human diet consists of a multitude of components, and there is a need to elucidate how certain compounds interact in collaboration. Withaferin A (WA), found in the Indian winter cherry and documented as a DNA methyltransferase (DNMT) inhibitor, and sulforaphane (SFN), a well-known histone deacetylase (HDAC) inhibitor found in cruciferous vegetables, are two epigenetic modifying compounds that have only recently been studied in conjunction...
April 21, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29688808/dna-methylation-and-the-potential-role-of-demethylating-agents-in-prevention-of-progressive-chronic-kidney-disease
#14
Benjamin P Larkin, Sarah J Glastras, Hui Chen, Carol A Pollock, Sonia Saad
Chronic kidney disease (CKD) is a global epidemic, and its major risk factors include obesity and type 2 diabetes. Obesity not only promotes metabolic dysregulation and the development of diabetic kidney disease but also may independently lead to CKD by a variety of mechanisms, including endocrine and metabolic dysfunction, inflammation, oxidative stress, altered renal hemodynamics, and lipotoxicity. Deleterious renal effects of obesity can also be transmitted from one generation to the next, and it is increasingly recognized that offspring of obese mothers are predisposed to CKD...
April 24, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29688621/an-epigenetic-signature-in-adipose-tissue-is-linked-to-nicotinamide-n-methyltransferase-gene-expression
#15
Ana B Crujeiras, Pavlos Pissios, Jose M Moreno-Navarrete, Angel Diaz-Lagares, Juan Sandoval, Antonio Gomez, Wilfredo Ricart, Manel Esteller, Felipe F Casanueva, Jose M Fernandez-Real
SCOPE: The enzyme nicotinamide N-methyltransferase (NNMT) is a major methyltransferase in adipose tissue. We hypothesized an epigenetic signature in association with NNMT gene expression in adipose tissue. METHODS AND RESULTS: The global human methylome was analyzed in visceral adipose tissue (VAT) from morbidly obese patients using the Infinium HumanMethylation450 BeadChip array (discovery cohort: n  =  11). The findings were confirmed in two additional independent cohorts (Cohort 1: n  =  60; BMI 20-60 kg/m2 and cohort 2: n  =  40; BMI >40 kg/m2 ) and validated after weight loss (using microarray data)...
April 24, 2018: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/29688601/de-novo-mutations-in-the-set-nuclear-proto-oncogene-encoding-a-component-of-the-inhibitor-of-histone-acetyltransferases-inhat-complex-in-patients-with-non-syndromic-intellectual-disability
#16
Servi Jc Stevens, Vyne van der Schoot, Magalie S Leduc, Tuula Rinne, Seema R Lalani, Marjan M Weiss, Johanna M van Hagen, Augusta Ma Lachmeijer, Sylvia G Stockler-Ipsiroglu, Anna Lehman, Han G Brunner
The role of disturbed chromatin remodelling in the pathogenesis of intellectual disability (ID) is well established and illustrated by de novo mutations found in a plethora of genes encoding for proteins of the epigenetic regulatory machinery. We describe mutations in the "SET nuclear proto-oncogene" (SET), encoding a component of the "inhibitor of acetyltransferases" (INHAT) complex, involved in transcriptional silencing. Using whole exome sequencing, four patients were identified with de novo mutations in the SET gene...
April 24, 2018: Human Mutation
https://www.readbyqxmd.com/read/29688592/stress-induced-evolution-of-herbicide-resistance-and-related-pleiotropic-effects
#17
REVIEW
William Edward Dyer
Herbicide-resistant weeds, especially those with resistance to multiple herbicides, represent a growing worldwide threat to agriculture and food security. Natural selection for resistant genotypes may act on standing genetic variation, or on a genetic and physiological background that is fundamentally altered because of stress responses to sublethal herbicide exposure. Stress-induced changes include DNA mutations, epigenetic alterations, transcriptional remodeling, and protein modifications, all of which can lead to herbicide resistance and a wide range of pleiotropic effects...
April 24, 2018: Pest Management Science
https://www.readbyqxmd.com/read/29688518/analysis-of-the-draft-genome-of-the-red-seaweed-gracilariopsis-chorda-provides-insights-into-genome-size-evolution-in-rhodophyta
#18
JunMo Lee, Eun Chan Yang, Louis Graf, Ji Hyun Yang, Huan Qiu, Udi Zel Zion, Cheong Xin Chan, Timothy G Stephens, Andreas P M Weber, Ga Hun Boo, Sung Min Boo, Kyeong Mi Kim, Younhee Shin, Myunghee Jung, Seung Jae Lee, Hyung-Soon Yim, Jung-Hyun Lee, Debashish Bhattacharya, Hwan Su Yoon
Red algae (Rhodophyta) underwent two phases of large-scale genome reduction during their early evolution. The red seaweeds did not attain genome sizes or gene inventories typical of other multicellular eukaryotes. We generated a high quality 92.1 Mbp draft genome assembly from the red seaweed Gracilariopsis chorda, including methylation and small (s)RNA data. We analyzed these and other Archaeplastida genomes to address three questions: 1) what is the role of repeats and transposable elements (TEs) in explaining Rhodophyta genome size variation, 2) what is the history of genome duplication and gene family expansion/reduction in these taxa, and 3) is there evidence for TE suppression in red algae? We find the number of predicted genes in red algae is relatively small (4,803-13,125 genes), particularly when compared to land plants, with no evidence of polyploidization...
April 23, 2018: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/29688306/emudra-ensemble-of-multiple-drug-repositioning-approaches-to-improve-prediction-accuracy
#19
Xianxiao Zhou, Minghui Wang, Igor Katsyv, Hanna Irie, Bin Zhang
Motivation: Availability of large-scale genomic, epigenetic and proteomic data in complex diseases makes it possible to objectively and comprehensively identify therapeutic targets that can lead to new therapies. The Connectivity Map has been widely used to explore novel indications of existing drugs. However, the prediction accuracy of the existing methods, such as Kolmogorov-Smirnov statistic remains low. Here we present a novel high-performance drug repositioning approach that improves over the state-of-the-art methods...
April 24, 2018: Bioinformatics
https://www.readbyqxmd.com/read/29688033/parvalbumin-promoter-hypermethylation-in-postmortem-brain-in-schizophrenia
#20
Helene A Fachim, Umarat Srisawat, Caroline F Dalton, Gavin P Reynolds
Deficits of brain parvalbumin (PV) are a consistent finding in schizophrenia and models of psychosis. We investigated whether this is associated with abnormal PV gene (PVALB) methylation in the brain in schizophrenia. Bisulfite pyrosequencing was used to determine cytosine (CpG) methylation in a PVALB promoter sequence. Greater PVALB methylation was found in schizophrenia hippocampus, while no differences were observed in prefrontal cortex. LINE-1 methylation, a measure of global methylation, was also elevated in both regions in schizophrenia, although the PVALB change was independent of this effect...
April 24, 2018: Epigenomics
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