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epigenetic silence

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https://www.readbyqxmd.com/read/28212378/sequencing-the-extrachromosomal-circular-mobilome-reveals-retrotransposon-activity-in-plants
#1
Sophie Lanciano, Marie-Christine Carpentier, Christel Llauro, Edouard Jobet, Dagmara Robakowska-Hyzorek, Eric Lasserre, Alain Ghesquière, Olivier Panaud, Marie Mirouze
Retrotransposons are mobile genetic elements abundant in plant and animal genomes. While efficiently silenced by the epigenetic machinery, they can be reactivated upon stress or during development. Their level of transcription not reflecting their transposition ability, it is thus difficult to evaluate their contribution to the active mobilome. Here we applied a simple methodology based on the high throughput sequencing of extrachromosomal circular DNA (eccDNA) forms of active retrotransposons to characterize the repertoire of mobile retrotransposons in plants...
February 17, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28210910/astrocyte-induced-reelin-expression-drives-proliferation-of-her2-breast-cancer-metastases
#2
Rahul Jandial, Cecilia Choy, Danielle M Levy, Mike Y Chen, Khairul I Ansari
Breast cancer metastasis to the brain develops after a clinical latency of years to even decades, suggesting that colonization of the brain is the most challenging step of the metastatic cascade. However, the underlying mechanisms used by breast cancer cells to successfully colonize the brain's microenvironment remain elusive. Reelin is an archetypal extracellular glycoprotein that regulates migration, proliferation, and lamination of neurons. It is epigenetically silenced in various cancers, and its expression in multiple myelomas is linked to poor patient survival...
February 17, 2017: Clinical & Experimental Metastasis
https://www.readbyqxmd.com/read/28198667/pan-cancer-analysis-of-frequent-dna-co-methylation-patterns-reveals-consistent-epigenetic-landscape-changes-in-multiple-cancers
#3
Jie Zhang, Kun Huang
BACKGROUND: DNA methylation is the major form of epigenetic modifications through which the cell regulates the gene expression and silencing. There have been extensive studies on the roles of DNA methylation in cancers, and several cancer drugs were developed targeting this process. However, DNA co-methylation cluster has not been examined in depth, and co-methylation in multiple cancer types has never been studied previously. RESULTS: In this study, we applied newly developed lmQCM algorithm to mine co-methylation clusters using methylome data from 11 cancer types in TCGA database, and found frequent co-methylated gene clusters exist in these cancer types...
January 25, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28198450/identification-of-methylation-driven-differentially-expressed-stxbp6-as-a-novel-biomarker-in-lung-adenocarcinoma
#4
Govinda Lenka, Mong-Hsun Tsai, Hsin-Chieh Lin, Jen-Hao Hsiao, Yi-Ching Lee, Tzu-Pin Lu, Jang-Ming Lee, Chung-Ping Hsu, Liang-Chuan Lai, Eric Y Chuang
DNA methylation is an essential epigenetic marker associated with the silencing of gene expression. Although various genome-wide studies revealed aberrantly methylated gene targets as molecular biomarkers for early detection, the survival rate of lung cancer patients is still poor. In order to identify methylation-driven biomarkers, genome-wide changes in DNA methylation and differential expression in 32 pairs of lung adenocarcinoma and adjacent normal lung tissue in non-smoking women were examined. This concurrent analysis identified 21 negatively correlated probes (r ≤ -0...
February 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28197553/the-role-of-sirt1-in-epileptogenesis
#5
Alicia M Hall, Gary P Brennan, Tiffany M Nguyen, Akanksha Singh-Taylor, Hyun-Seung Mun, Mary J Sargious, Tallie Z Baram
The mechanisms by which brain insults lead to subsequent epilepsy remain unclear. Insults, including trauma, stroke, tumors, infections, and long seizures [status epilepticus (SE)], create a neuronal state of increased metabolic demand or decreased energy supply. Neurons express molecules that monitor their metabolic state, including sirtuins (Sirts). Sirtuins deacetylate cytoplasmic proteins and nuclear histones, and their epigenetic modulation of the chromatin governs the expression of many genes, influencing neuronal properties...
January 2017: ENeuro
https://www.readbyqxmd.com/read/28195240/mir302-regulates-snai1-expression-to-control-mesangial-cell-plasticity
#6
L De Chiara, D Andrews, A Watson, G Oliviero, G Cagney, J Crean
Cell fate decisions are controlled by the interplay of transcription factors and epigenetic modifiers, which together determine cellular identity. Here we elaborate on the role of miR302 in the regulation of cell plasticity. Overexpression of miR302 effected silencing of the TGFβ type II receptor and facilitated plasticity in a manner distinct from pluripotency, characterized by increased expression of Snail. miR302 overexpressing mesangial cells also exhibited enhanced expression of EZH2 coincident with Snail upregulation...
February 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28193854/gene-activation-of-smn-by-selective-disruption-of-lncrna-mediated-recruitment-of-prc2-for-the-treatment-of-spinal-muscular-atrophy
#7
Caroline J Woo, Verena K Maier, Roshni Davey, James Brennan, Guangde Li, John Brothers, Brian Schwartz, Susana Gordo, Anne Kasper, Trevor R Okamoto, Hans E Johansson, Berhan Mandefro, Dhruv Sareen, Peter Bialek, B Nelson Chau, Balkrishen Bhat, David Bullough, James Barsoum
Spinal muscular atrophy (SMA) is a neurodegenerative disease characterized by progressive motor neuron loss and caused by mutations in SMN1 (Survival Motor Neuron 1). The disease severity inversely correlates with the copy number of SMN2, a duplicated gene that is nearly identical to SMN1. We have delineated a mechanism of transcriptional regulation in the SMN2 locus. A previously uncharacterized long noncoding RNA (lncRNA), SMN-antisense 1 (SMN-AS1), represses SMN2 expression by recruiting the Polycomb Repressive Complex 2 (PRC2) to its locus...
February 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28193828/epigenetic-component-p66a-modulates-myeloid-derived-suppressor-cells-by-modifying-stat3
#8
Jiaxuan Xin, Zhiqian Zhang, Xiaomin Su, Liyang Wang, Yuan Zhang, Rongcun Yang
STAT3 plays a critical role in myeloid-derived suppressor cell (MDSC) accumulation and activation. Most studies have probed underlying mechanisms of STAT3 activation. However, epigenetic events involved in STAT3 activation are poorly understood. In this study, we identified several epigenetic-associated proteins such as p66a (Gatad2a), a novel protein transcriptional repressor that might interact with STAT3 in functional MDSCs, by using immunoprecipitation and mass spectrometry. p66a could regulate the phosphorylation and ubiquitination of STAT3...
February 13, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28193737/exogenous-transposable-elements-circumvent-identity-based-silencing-permitting-the-dissection-of-expression-dependent-silencing
#9
Dalen Fultz, R Keith Slotkin
The propagation of epigenetic marks has received a great deal of attention, yet the initiation of epigenetic silencing of a new transgene, virus, or transposable element (TE) remains enigmatic. The overlapping and simultaneous function of multiple silencing mechanisms has obscured this area of investigation. Here, we have revealed two broad mechanisms that can initiate silencing independently: identity-based and expression-dependent silencing. We found that identity-based silencing is targeted by 21-22 or 24 nucleotide small interfering RNAs (siRNAs) generated from previously silenced regions of the genome...
February 13, 2017: Plant Cell
https://www.readbyqxmd.com/read/28188746/context-dependent-epigenetic-regulation-of-nuclear-factor-of-activated-t-cells-1-in-pancreatic-plasticity
#10
Nai-Ming Chen, Albrecht Neesse, Moritz Lino Dyck, Benjamin Steuber, Alexander O Koenig, Clara Lubeseder-Martellato, Thore Winter, Teresa Forster, Hanibal Bohnenberger, Julia Kitz, Kirsten-Reuter Jessen, Heidi Griesmann, Jochen Gaedcke, Marian Grade, Jin-San Zhang, Wan-Chi Tsai, Jens Siveke, Hans-Ulrich Schildhaus, Philipp Ströbel, Steven A Johnsen, Volker Ellenrieder, Elisabeth Hessmann
BACKGROUND & AIMS: The ability of exocrine pancreatic cells to change the cellular phenotype is required for tissue regeneration upon injury but also contributes to their malignant transformation and tumor progression. We investigated context-dependent signaling and transcription mechanisms that determine pancreatic cell fate decisions toward regeneration and malignancy. In particular, we studied the function and regulation of the inflammatory transcription factor nuclear factor of activated T cells 1 (NFATC1) in pancreatic cell plasticity and tissue adaptation...
February 7, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28182006/coordinate-activities-of-brd4-and-cdk9-in-the-transcriptional-elongation-complex-are-required-for-tgf%C3%AE-induced-nox4-expression-and-myofibroblast-transdifferentiation
#11
Talha Ijaz, Mohammad Jamaluddin, Yingxin Zhao, Yueqing Zhang, Jayson Jay, Celeste C Finnerty, David N Herndon, Ronald G Tilton, Allan R Brasier
Transdifferentiation of quiescent dermal fibroblasts to secretory myofibroblasts has a central role in wound healing and pathological scar formation. This myofibroblast transdifferentiation process involves TGFβ-induced de novo synthesis of alpha smooth muscle cell actin (αSMA)+ fibers that enhance contractility as well as increased expression of extracellular matrix (ECM) proteins, including collagen and fibronectin. These processes are mediated upstream by the reactive oxygen species (ROS)-producing enzyme Nox4, whose induction by TGFβ is incompletely understood...
February 9, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28178655/chl1-hypermethylation-as-a-potential-biomarker-of-poor-prognosis-in-breast-cancer
#12
Esperanza Martín-Sánchez, Saioa Mendaza, Ane Ulazia-Garmendia, Iñaki Monreal-Santesteban, Idoia Blanco-Luquin, Alicia Córdoba, Francisco Vicente-García, Noemí Pérez-Janices, David Escors, Diego Megías, Paula López-Serra, Manel Esteller, José Juan Illarramendi, David Guerrero-Setas
The CHL1 gene encodes a cell-adhesion molecule proposed as being a putative tumour-suppressor gene in breast cancer (BC). However, neither the underlying molecular mechanisms nor the clinical value of CHL1 downregulation in BC has been explored. The methylation status of three CpG sites in the CHL1 promoter was analysed by pyrosequencing in neoplastic biopsies from 142 patients with invasive BC and compared with that of non-neoplastic tissues. We found higher CHL1 methylation levels in breast tumours than in non-neoplastic tissues, either from mammoplasties or adjacent-to-tumour, which correlated with lower levels of protein expression in tumours measured by immunohistochemistry...
February 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28178526/crl4-dcaf8-ubiquitin-ligase-targets-histone-h3k79-and-promotes-h3k9-methylation-in-the-liver
#13
Gaofeng Li, Tong Ji, Jiang Chen, Yufei Fu, Lidan Hou, Yan Feng, Tingyue Zhang, Tianyu Song, Jie Zhao, Yoko Endo, Hui Lin, Xiujun Cai, Yong Cang
Transcription from chromosomes is regulated by posttranslational modifications to histones, such as methylation and ubiquitination. Monoubiquitination of histones H2A and H2B influences H3 methylation to reinforce the activation or repression of gene expression. Here, we provide evidence that H3 polyubiquitination represses transcription of fetal and cell-cycle genes in postnatal mouse liver by crosstalk with H3K9 methylation. We found that the CRL4 ubiquitin ligase targets H3 for polyubiquitination at K79 via the DCAF8 substrate receptor in hepatocytes...
February 7, 2017: Cell Reports
https://www.readbyqxmd.com/read/28176650/is-there-a-role-for-epigenetic-enhancement-of-immunomodulatory-approaches-to-cancer-treatment
#14
Kirsty J Flower, Sadaf Ghaem-Maghami, Robert Brown
The efficacy of cancer immunotherapy relies on the ability of the host immune system to recognise the cancer as non-self and eliminate it from the body. Whilst this is an extremely fertile area of medical research, with positive clinical trials showing durable responses, attention must be paid to the subset of patients that do not respond to these treatments. Immune surveillance and immunoediting by the host could itself select for immune-evasive tumour cells during tumour development leading to immunotherapy resistance...
February 5, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28157505/polycomb-repressive-complex-1-generates-discrete-compacted-domains-that-change-during-differentiation
#15
Sharmistha Kundu, Fei Ji, Hongjae Sunwoo, Gaurav Jain, Jeannie T Lee, Ruslan I Sadreyev, Job Dekker, Robert E Kingston
Master regulatory genes require stable silencing by the polycomb group (PcG) to prevent misexpression during differentiation and development. Some PcG proteins covalently modify histones, which contributes to heritable repression. The role for other effects on chromatin structure is less understood. We characterized the organization of PcG target genes in ESCs and neural progenitors using 5C and super-resolution microscopy. The genomic loci of repressed PcG targets formed discrete, small (20-140 Kb) domains of tight interaction that corresponded to locations bound by canonical polycomb repressive complex 1 (PRC1)...
February 2, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28157489/cathepsin-h-mediated-degradation-of-hdac4-for-matrix-metalloproteinase-expression-in-hepatic-stellate-cells-implications-of-epigenetic-suppression-of-matrix-metalloproteinases-in-fibrosis-through-stabilization-of-class-iia-histone-deacetylases
#16
Zemin Yang, Yu Liu, Lan Qin, Pengfei Wu, Zanxian Xia, Mei Luo, Yilan Zheng, Hidekazu Tsukamoto, Zongyun Ju, Danmei Su, Han Kang, Zhixiong Xiao, Sujun Zheng, Zhongping Duan, Richard Hu, Qiang Wang, Stephen J Pandol, Yuan-Ping Han
In three-dimensional extracellular matrix, mesenchymal cells including hepatic stellate cells (HSCs) gain the ability to express matrix metalloproteinases (MMPs) on injury signals. In contrast, in myofibroblastic HSCs in fibrotic liver, many MMP genes are silenced into an epigenetically nonpermissive state. The mechanism by which the three-dimensional extracellular matrix confers the MMP genes into an epigenetically permissive state has not been well characterized. In continuation of previous work, we show here that the up-regulation of MMP genes is mediated through degradation of class IIa histone deacetylases (HDACs) by certain cysteine cathepsins (Cts)...
January 31, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28154185/heterochromatin-protein-1%C3%AE-is-a-novel-epigenetic-repressor-of-human-embryonic-%C3%AF%C2%B5-globin-gene-expression
#17
Yadong Wang, Ying Wang, Lingling Ma, Min Nie, Junyi Ju, Ming Liu, Yexuan Deng, Bing Yao, Tao Gui, Xinyu Li, Chan Guo, Chi Ma, Renxiang Tan, Quan Zhao
Production of hemoglobin during development is tightly regulated. For example, expression from the human β-globin gene locus, comprising β-, δ-, ϵ-, and γ-globin genes, switches from ϵ-globin to γ-globin during embryonic development and then from γ-globin to β-globin after birth. Expression of human ϵ-globin in mice has been shown to ameliorate anemia caused by β-globin mutations, including those causing β-thalassemia and sickle cell disease (SCD), raising the prospect that reactivation of ϵ-globin expression could be used in managing these conditions in humans...
February 1, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28153411/linking-chromatin-fibers-to-gene-folding-by-hierarchical-looping
#18
REVIEW
Gavin Bascom, Tamar Schlick
While much is known about DNA structure on the basepair level, this scale represents only a fraction of the structural levels involved in folding the genomic material. With recent advances in experimental and theoretical techniques, a variety of structures have been observed on the fiber, gene, and chromosome levels of genome organization. Here we view chromatin architecture from nucleosomes and fibers to genes and chromosomes, highlighting the rich structural diversity and fiber fluidity emerging from both experimental and theoretical techniques...
February 7, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28152305/concurrent-hypermethylation-of-sfrp2-and-dkk2-activates-the-wnt-%C3%AE-catenin-pathway-and-is-associated-with-poor-prognosis-in-patients-with-gastric-cancer
#19
Hao Wang, Xiang-Long Duan, Xiao-Li Qi, Lei Meng, Yi-Song Xu, Tong Wu, Peng-Gao Dai
Aberrant hypermethylation of Wnt antagonists has been observed in gastric cancer. A number of studies have focused on the hypermethylation of a single Wnt antagonist and its role in regulating the activation of signaling. However, how the Wnt antagonists interacted to regulate the signaling pathway has not been reported. In the present study, we systematically investigated the methylation of some Wnt antagonist genes (SFRP2, SFRP4, SFRP5, DKK1, DKK2, and APC) and their regulatory role in carcinogenesis. We found that aberrant promoter methylation of SFRP2, SFRP4, DKK1, and DKK2 was significantly increased in gastric cancer...
January 2017: Molecules and Cells
https://www.readbyqxmd.com/read/28149335/cdh22-hypermethylation-is-an-independent-prognostic-biomarker-in-breast-cancer
#20
Esperanza Martín-Sánchez, Saioa Mendaza, Ane Ulazia-Garmendia, Iñaki Monreal-Santesteban, Alicia Córdoba, Francisco Vicente-García, Idoia Blanco-Luquin, Susana De La Cruz, Ana Aramendia, David Guerrero-Setas
BACKGROUND: Cadherin-like protein 22 (CDH22) is a transmembrane glycoprotein involved in cell-cell adhesion and metastasis. Its role in cancer is controversial because it has been described as being upregulated in colorectal cancer, whereas it is downregulated in metastatic melanoma. However, its status in breast cancer (BC) is unknown. The purpose of our study was to determine the molecular status and clinical value of CDH22 in BC. RESULTS: We observed by immunohistochemistry that the level of CDH22 expression was lower in BC tissues than in their matched adjacent-to-tumour and non-neoplastic tissues from reduction mammoplasties...
2017: Clinical Epigenetics
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