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Dna damage and epigenetic

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https://www.readbyqxmd.com/read/28934364/the-histone-variant-macroh2a-confers-functional-robustness-to-the-intestinal-stem-cell-compartment
#1
Ryan James Cedeno, Angela Nakauka-Ddamba, Maryam Yousefi, Stephanie Sterling, Nicolae Adrian Leu, Ning Li, John R Pehrson, Christopher Joachim Lengner
A stem cell's epigenome directs cell fate during development, homeostasis, and regeneration. Epigenetic dysregulation can lead to inappropriate cell fate decisions, aberrant cell function, and even cancer. The histone variant macroH2A has been shown to influence gene expression, guide cell fate, and safeguard against genotoxic stress. Interestingly, mice lacking functional macroH2A histones (hereafter referred to as macroH2A DKO) are viable and fertile; yet suffer from increased perinatal death and reduced weight and size compared to wildtype (WT)...
2017: PloS One
https://www.readbyqxmd.com/read/28927528/adaptation-of-the-human-population-to-the-environment-current-knowledge-clues-from-czech-cytogenetic-and-omics-biomonitoring-studies-and-possible-mechanisms
#2
REVIEW
Andrea Rossnerova, Michaela Pokorna, Vlasta Svecova, Radim J Sram, Jan Topinka, Friedo Zölzer, Pavel Rossner
The human population is continually exposed to numerous harmful environmental stressors, causing negative health effects and/or deregulation of biomarker levels. However, studies reporting no or even positive impacts of some stressors on humans are also sometimes published. The main aim of this review is to provide a comprehensive overview of the last decade of Czech biomonitoring research, concerning the effect of various levels of air pollution (benzo[a]pyrene) and radiation (uranium, X-ray examination and natural radon background), on the differently exposed population groups...
July 2017: Mutation Research
https://www.readbyqxmd.com/read/28920955/mir-25-93-mediates-hypoxia-induced-immunosuppression-by-repressing-cgas
#3
Min-Zu Wu, Wei-Chung Cheng, Su-Feng Chen, Shin Nieh, Carolyn O'Connor, Chia-Lin Liu, Wen-Wei Tsai, Cheng-Jang Wu, Lorena Martin, Yaoh-Shiang Lin, Kou-Juey Wu, Li-Fan Lu, Juan Carlos Izpisua Belmonte
The mechanisms by which hypoxic tumours evade immunological pressure and anti-tumour immunity remain elusive. Here, we report that two hypoxia-responsive microRNAs, miR-25 and miR-93, are important for establishing an immunosuppressive tumour microenvironment by downregulating expression of the DNA sensor cGAS. Mechanistically, miR-25/93 targets NCOA3, an epigenetic factor that maintains basal levels of cGAS expression, leading to repression of cGAS during hypoxia. This allows hypoxic tumour cells to escape immunological responses induced by damage-associated molecular pattern molecules, specifically the release of mitochondrial DNA...
September 18, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28915699/biological-effects-and-epidemiological-consequences-of-arsenic-exposure-and-reagents-that-can-ameliorate-arsenic-damage-in-vivo
#4
REVIEW
Chinthalapally V Rao, Sanya Pal, Altaf Mohammed, Mudassir Farooqui, Mark P Doescher, Adam S Asch, Hiroshi Y Yamada
Through contaminated diet, water, and other forms of environmental exposure, arsenic affects human health. There are many U.S. and worldwide "hot spots" where the arsenic level in public water exceeds the maximum exposure limit. The biological effects of chronic arsenic exposure include generation of reactive oxygen species (ROS), leading to oxidative stress and DNA damage, epigenetic DNA modification, induction of genomic instability, and inflammation and immunomodulation, all of which can initiate carcinogenesis...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915585/time-dependent-modulation-of-tumor-radiosensitivity-by-a-pan-hdac-inhibitor-abexinostat
#5
Sofia Rivera, Céline Leteur, Frédérique Mégnin, Frédéric Law, Isabelle Martins, Ioana Kloos, Stéphane Depil, Nazanine Modjtahedi, Jean Luc Perfettini, Christophe Hennequin, Eric Deutsch
Despite prominent role of radiotherapy in lung cancer management, there is an urgent need for strategies increasing therapeutic efficacy. Reversible epigenetic changes are promising targets for combination strategies using HDAC inhibitors (HDACi). Here we evaluated on two NSCLC cell lines, the antitumor effect of abexinostat, a novel pan HDACi combined with irradiation in vitro in normoxia and hypoxia, by clonogenic assays, demonstrating that abexinostat enhances radiosensitivity in a time dependent way with mean SER10 between 1...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28912501/transcription-regulation-of-cdkn1a-p21-cip1-waf1-by-trf2-is-epigenetically-controlled-through-the-rest-repressor-complex
#6
Tabish Hussain, Dhurjhoti Saha, Gunjan Purohit, Anirban Kar, Anand Kishore Mukherjee, Shalu Sharma, Suman Sengupta, Parashar Dhapola, Basudeb Maji, Sreekanth Vedagopuram, Nobuko T Horikoshi, Nobuo Horikoshi, Raj K Pandita, Santanu Bhattacharya, Avinash Bajaj, Jean-François Riou, Tej K Pandita, Shantanu Chowdhury
We observed extra-telomeric binding of the telomere repeat binding factor TRF2 within the promoter of the cyclin-dependent kinase CDKNIA (p21/CIP1/WAF1). This result in TRF2 induced transcription repression of p21. Interestingly, p21 repression was through engagement of the REST-coREST-LSD1-repressor complex and altered histone marks at the p21 promoter in a TRF2-dependent fashion. Furthermore, mutational analysis shows p21 repression requires interaction of TRF2 with a p21 promoter G-quadruplex. Physiologically, TRF2-mediated p21 repression attenuated drug-induced activation of cellular DNA damage response by evading G2/M arrest in cancer cells...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28912174/senescence-is-a-spi1-pu-1-induced-anti-proliferative-mechanism-in-primary-hematopoietic-cells
#7
Laure Delestré, Cui Hengxiang, Michela Esposito, Cyril Quiveron, Elena Mylonas, Virginie Penard-Lacronique, Oliver Bischof, Christel Guillouf
Transcriptional deregulation caused by epigenetic or genetic alterations is a major cause of leukemic transformation. The Spi1/PU.1 transcription factor is a key regulator of many steps of hematopoiesis, and limits self-renewal of hematopoietic stem cells. The deregulation of its expression or activity contributes to leukemia, in which Spi1 can be either an oncogene or a tumor suppressor. Here, we explored whether cellular senescence, an anti-tumoral pathway that restrains cell proliferation, is a mechanism by which Spi1 limits hematopoietic cells expansion, and thus prevents the development of leukemia...
September 14, 2017: Haematologica
https://www.readbyqxmd.com/read/28911547/multifunctions-of-dietary-polyphenols-in-the-regulation-of-intestinal-inflammation
#8
REVIEW
Makoto Shimizu
Food for specified health use is a type of functional food approved by the Japanese government, with more than 1250 products in 10 health-claim categories being approved as of April 2016. Polyphenols are currently used as functional ingredients in seven of the 10 categories. Although they have not yet been used for the food-for-specified-health-use category of "gut health promotion," polyphenols are expected to contribute to the future development of gut-modulating food. Intestinal functions include digestion/absorption, acting as a barrier, recognition of external factors, and signal transduction...
January 2017: Journal of Food and Drug Analysis
https://www.readbyqxmd.com/read/28904641/histone-code-and-long-non-coding-rnas-lncrnas-aberrations-in-lung-cancer-implications-in-the-therapy-response
#9
REVIEW
Abril Marcela Herrera-Solorio, Leonel Armas-López, Oscar Arrieta, Joaquín Zúñiga, Patricia Piña-Sánchez, Federico Ávila-Moreno
Respiratory diseases hold several genome, epigenome, and transcriptional aberrations as a cause of the accumulated damage promoted by, among others, environmental risk factors. Such aberrations can also come about as an adaptive response when faced with therapeutic oncological drugs. In epigenetic terms, aberrations in DNA methylation patterns, histone code marks balance, and/or chromatin-remodeling complexes recruitment, among Polycomb Repressive Complex-2 (PRC2) versus Trithorax (TRX) Activator Complex, have been proposed to be affected by several previously characterized functional long non-coding RNAs (lncRNAs)...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28866885/targeted-proteomic-analyses-of-histone-h4-acetylation-changes-associated-with-homologous-recombination-deficient-high-grade-serous-ovarian-carcinomas
#10
Stefani N Thomas, Lijun Chen, Yang Liu, Naseruddin Höti, Hui Zhang
Approximately 20% of high-grade serous ovarian cancers are homologous-recombination (HR)-deficient due to genetic and epigenetic mutations of HR pathway genes including the tumor suppressor genes BRCA1 and 2. HR deficiency (HRD) compromises cells' ability to efficiently repair DNA damage, but it also increases sensitivity to chemotherapeutic treatment strategies; however, not all ovarian cancer patients with HRD tumors exhibit positive responses to chemotherapy. Our previous iTRAQ-based comprehensive proteomic characterization of high-grade serous ovarian carcinomas found that lower levels of histone H4 acetylation at Lys12 and Lys16 (H4-K12acK16ac) were associated with HRD tumors compared with non-HRD tumors...
September 14, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28864287/age-related-cataracts-role-of-unfolded-protein-response-ca-2-mobilization-epigenetic-dna-modifications-and-loss-of-nrf2-keap1-dependent-cytoprotection
#11
REVIEW
Palsamy Periyasamy, Toshimichi Shinohara
Age-related cataracts are closely associated with lens chronological aging, oxidation, calcium imbalance, hydration and crystallin modifications. Accumulating evidence indicates that misfolded proteins are generated in the endoplasmic reticulum (ER) by most cataractogenic stresses. To eliminate misfolded proteins from cells before they can induce senescence, the cells activate a clean-up machinery called the ER stress/unfolded protein response (UPR). The UPR also activates the nuclear factor-erythroid-2-related factor 2 (Nrf2), a central transcriptional factor for cytoprotection against stress...
September 2017: Progress in Retinal and Eye Research
https://www.readbyqxmd.com/read/28859669/epigenetic-silencing-of-mir-493-increases-the-resistance-to-cisplatin-in-lung-cancer-by-targeting-tongue-cancer-resistance-related-protein-1-tcrp1
#12
Yixue Gu, Zhijie Zhang, Jiang Yin, Jiahui Ye, Yin Song, Hao Liu, Yan Xiong, Minying Lu, Guopei Zheng, Zhimin He
BACKGROUND: The potential mechanisms regarding how methylation of microRNA(miRNA) CpG Island could regulate cancer cell chemo-resistance remains unclear. This study aims to explore the epigenetic dysregulation mechanism of miRNA-493 and the ability to modulate lung cancer cell chemotherapy resistance. METHODS: Real-time quantitative PCR (qRT-PCR) and In situ hybridization (ISH) were used to analyze the expression of miR-493 in lung cancer cell lines and tumor tissue, respectively...
August 31, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28857308/a-novel-splicing-isoform-of-protein-arginine-methyltransferase-1-prmt1-that-lacks-the-dimerization-arm-and-correlates-with-cellular-malignancy
#13
Odysseas Patounas, Ioanna Papacharalampous, Carmen Eckerich, Georgios S Markopoulos, Evangelos Kolettas, Frank O Fackelmayer
Methylation of arginine residues is an important modulator of protein function that is involved in epigenetic gene regulation, DNA damage response and RNA maturation, as well as in cellular signaling. The enzymes that catalyze this post-translational modification are called protein arginine methyltransferases (PRMTs), of which PRMT1 is the predominant enzyme. Human PRMT1 has previously been shown to occur in seven splicing isoforms, which are differentially abundant in different tissues, and have distinct substrate specificity and intracellular localization...
August 31, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28842808/evaluation-of-dna-methylation-and-mrna-expression-of-heat-shock-proteins-in-thermal-manipulated-chicken
#14
A Vinoth, T Thirunalasundari, M Shanmugam, A Uthrakumar, S Suji, U Rajkumar
Thermal manipulation during embryogenesis has been demonstrated to enhance the thermotolerance capacity of broilers through epigenetic modifications. Heat shock proteins (HSPs) are induced in response to stress for guarding cells against damage. The present study investigates the effect of thermal conditioning during embryogenesis and thermal challenge at 42 days of age on HSP gene and protein expression, DNA methylation and in vitro luciferase assay in brain tissue of Naked Neck (NN) and Punjab Broiler-2 (PB-2) chicken...
August 25, 2017: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/28842529/structure-of-the-holliday-junction-applications-beyond-recombination
#15
REVIEW
P Shing Ho
The Holliday junction (HJ) is an essential element in recombination and related mechanisms. The structure of this four-stranded DNA assembly, which is now well-defined alone and in complex with proteins, has led to its applications in areas well outside of molecular recombination, including nanotechnology and biophysics. This minireview explores some interesting recent research on the HJ, as it has been adapted to design regular two- or three-dimensional lattices for crystal engineering, and more complex systems through DNA origami...
August 24, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28832971/class-i-hdac-inhibition-improves-pancreatitis-outcome-by-limiting-leukocyte-recruitment-and-acinar-to-ductal-metaplasia
#16
Marta Bombardo, Enrica Saponara, Ermanno Malagola, Rong Chen, Gitta M Seleznik, Cecile Haumaitre, Evans Quilichini, Anja Zabel, Theresia Reding, Rolf Graf, Sabrina Sonda
BACKGROUND AND PURPOSE: Pancreatitis is a common inflammation of the pancreas with rising incidence in many countries. Despite improvements in diagnostic techniques, the disease is associated with high risk of severe morbidity and mortality and there is an urgent need for new therapeutic interventions. In this study we evaluated whether histone deacetylases (HDACs), key epigenetic regulators of gene transcription, are involved in the development of the disease. EXPERIMENTAL APPROACH: We analyzed HDAC regulation during cerulein-induced acute, chronic and autoimmune pancreatitis using different transgenic mouse models...
August 17, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28831923/the-food-and-drug-addiction-epidemic-targeting-dopamine-homeostasis
#17
Kenneth Blum, Panayotis K Thanos, Gene-Jack Wang, Marcelo Febo, Zsolt Demetrovics, Edward Justin Modestino, Eric R Braverman, David Baron, Rajendra D Badgaiyan, Mark S Gold
Obesity is damaging the lives of more than 300 million people worldwide and maintaining a healthy weight using popular weight loss tactics remains a very difficult undertaking. Managing the obesity problem seems within reach, as better understanding develops, of the function of our genome in drug/nutrient responses. Strategies indicated by this understanding of nutriepigenomics and neurogenetics in the treatment and prevention of metabolic syndrome and obesity include moderation of mRNA expression by DNA methylation, and inhibition of histone deacetylation...
August 22, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28819832/protective-role-of-humic-acids-against-picloram-induced-genomic-instability-and-dna-methylation-in-phaseolus-vulgaris
#18
Mahmut Sinan Taspinar, Murat Aydin, Burcu Sigmaz, Nalan Yildirim, Guleray Agar
Picloram (4-amino-3,5,6-trichloropicolinic acid) is a liquid auxinic herbicide used to control broad-leaved weeds. Picloram is representing a possible hazard to ecosystems and human health. Therefore, in this study, DNA methylation changes and DNA damage levels in Phaseolus vulgaris exposed to picloram, as well as whether humic acid (HA) has preventive effects on these changes were investigated. Random amplified polymorphic DNA (RAPD) techniques were used for identification of DNA damage and coupled restriction enzyme digestion-random amplification (CRED-RA) techniques were used to detect the changed pattern of DNA methylation...
August 17, 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/28811345/inhibitors-of-the-histone-methyltransferases-ezh2-1-induce-a-potent-antiviral-state-and-suppress-infection-by-diverse-viral-pathogens
#19
Jesse H Arbuckle, Paul J Gardina, David N Gordon, Heather D Hickman, Jonathan W Yewdell, Theodore C Pierson, Timothy G Myers, Thomas M Kristie
Epigenetic regulation is based on a network of complexes that modulate the chromatin character and structure of the genome to impact gene expression, cell fate, and development. Thus, epigenetic modulators represent novel therapeutic targets used to treat a range of diseases, including malignancies. Infectious pathogens such as herpesviruses are also regulated by cellular epigenetic machinery, and epigenetic therapeutics represent a novel approach used to control infection, persistence, and the resulting recurrent disease...
August 15, 2017: MBio
https://www.readbyqxmd.com/read/28809938/perinatal-testosterone-exposure-potentiates-vascular-dysfunction-by-er%C3%AE-suppression-in-endothelial-progenitor-cells
#20
Weiguo Xie, Mingming Ren, Ling Li, Yin Zhu, Zhigang Chu, Zhigang Zhu, Qiongfang Ruan, Wenting Lou, Haimou Zhang, Zhen Han, Xiaodong Huang, Wei Xiang, Tao Wang, Paul Yao
Recent clinical cohort study shows that testosterone therapy increases cardiovascular diseases in men with low testosterone levels, excessive circulating androgen levels may play a detrimental role in the vascular system, while the potential mechanism and effect of testosterone exposure on the vascular function in offspring is still unknown. Our preliminary results showed that perinatal testosterone exposure in mice induces estrogen receptor β (ERβ) suppression in endothelial progenitor cells (EPCs) in offspring but not mothers, while estradiol (E2) had no effect...
2017: PloS One
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