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Dna damage and epigenetic

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https://www.readbyqxmd.com/read/29348130/setd1a-protects-hscs-from-activation-induced-functional-decline-in-vivo
#1
Kathrin Arndt, Andrea Kranz, Juliane Fohgrub, Adrien Jolly, Anita S Bledau, Michela Di Virgilio, Mathias Lesche, Andreas Dahl, Thomas Höfer, A Francis Stewart, Claudia Waskow
The regenerative capacity of hematopoietic stem cells (HSCs) is limited by the accumulation of DNA damage. Conditional mutagenesis of the histone 3 lysine 4 (H3K4) methyltransferase, Setd1a, revealed that it is required for the expression of DNA damage recognition and repair pathways in HSCs. Specific deletion of Setd1a in adult long-term (LT)-HSCs is compatible with adult life and has little effect on the maintenance of phenotypic LT-HSCs in the bone marrow. However, SETD1A-deficient LT-HSCs lose their transcriptional cellular identity accompanied by loss of their proliferative capacity and stem cell function under replicative stress in situ and after transplantation...
January 18, 2018: Blood
https://www.readbyqxmd.com/read/29318979/role-of-epigenetics-and-oxidative-stress-in-gliomagenesis
#2
Edgar Rangel-Lopez, Yesennia Sanchez-Perez, Ernesto Soto-Reyes, Claudia Maria Garcia-Cuellar, Bernardo Cacho-Diaz, Abel Santamaria
Malignant gliomas constitute more than 49% of all central nervous system (CNS) tumors and exhibit very poor prognosis. Two main events involved with the progression of gliomas are the deregulation of genes by genetic events and cellular damage elicited by the formation of reactive oxygen species (ROS). In gliomas, epigenetic abnormalities implicated in the deregulation of DNA methylation, nucleosome rearrangement, and acetylation of histones have been depicted. The overproduction of ROS has been implicated in the promotion of these modifications...
January 10, 2018: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/29311218/sirt1-a-guardian-of-the-development-of-diabetic-retinopathy
#3
Manish Mishra, Arul J Duraisamy, Renu A Kowluru
Diabetic retinopathy is a multifactorial disease, and the exact mechanism of its pathogenesis remains obscure. A multifunctional deacetylase Sirtuin 1 (Sirt1), is implicated in regulation of many cellular functions and transcription of genes, and retinal Sirt1 is inhibited in diabetes. Our aim is to determine the role of Sirt1 in the development of diabetic retinopathy, and elucidate the molecular mechanism of its downregulation. Using mice overexpressing Sirt1, diabetic for 8 month, structural, functional and metabolic abnormalities were investigated in vascular and neuronal retina...
January 8, 2018: Diabetes
https://www.readbyqxmd.com/read/29305001/epigenetic-regulation-of-adult-myogenesis
#4
Daniel C L Robinson, Francis J Dilworth
Skeletal muscle regeneration is an efficient stem cell-based repair system that ensures healthy musculature. For this repair system to function continuously throughout life, muscle stem cells must contribute to the process of myofiber repair as well as repopulation of the stem cell niche. The decision made by the muscle stem cells to commit to the muscle repair or to remain a stem cell depends upon patterns of gene expression, a process regulated at the epigenetic level. Indeed, it is well accepted that dynamic changes in epigenetic landscapes to control DNA accessibility and expression is a critical component during myogenesis for the effective repair of damaged muscle...
2018: Current Topics in Developmental Biology
https://www.readbyqxmd.com/read/29303998/linking-dna-damage-and-age-related-promoter-dna-hyper-methylation-in-the-intestine
#5
Torsten Thalheim, Maria Herberg, Joerg Galle
Aberrant DNA methylation in stem cells is a hallmark of aging and tumor development. Here, we explore whether and how DNA damage repair might impact on these time-dependent changes, in particular in proliferative intestinal stem cells. We introduce a 3D multiscale computer model of intestinal crypts enabling simulation of aberrant DNA and histone methylation of gene promoters during aging. We assume histone state-dependent activity of de novo DNA methyltransferases (DNMTs) and methylation-dependent binding of maintenance DNMTs to CpGs...
January 5, 2018: Genes
https://www.readbyqxmd.com/read/29302192/identification-of-epigenetically-altered-genes-and-potential-gene-targets-in-melanoma-using-bioinformatic-methods
#6
Honghao Duan, Ke Jiang, Dengke Wei, Lijun Zhang, Deliang Cheng, Min Lv, Yuben Xu, Aimin He
This study aimed to analyze epigenetically and genetically altered genes in melanoma to get a better understanding of the molecular circuitry of melanoma and identify potential gene targets for the treatment of melanoma. The microarray data of GSE31879, including mRNA expression profiles (seven melanoma and four melanocyte samples) and DNA methylation profiles (seven melanoma and five melanocyte samples), were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) and differentially methylated positions (DMPs) were screened using the linear models for microarray data (limma) package in melanoma compared with melanocyte samples...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29287311/hypomethylation-of-cyp2e1-and-dusp22-promoters-associated-with-disease-activity-and-erosive-disease-among-rheumatoid-arthritis-patients
#7
Amanda Mok, Brooke Rhead, Calliope Holingue, Xiaorong Shao, Hong L Quach, Diana Quach, Elizabeth Sinclair, Jonathan Graf, John Imboden, Thomas Link, Ruby Harrison, Vladimir Chernitskiy, Lisa F Barcellos, Lindsey A Criswell
OBJECTIVE: Epigenetic modifications have previously been associated with rheumatoid arthritis (RA). This study aimed to determine whether differential DNA methylation in peripheral blood cell subpopulations is associated with four clinical outcomes among RA patients. METHODS: Peripheral blood samples were taken from 63 patients in the University of California, San Francisco RA cohort (all satisfied ACR classification criteria; 57 were seropositive). Cells were FACS-sorted into four immune cell subpopulations (CD14+ monocytes, CD19+ B cells, CD4+ naïve T cells, and CD4+ memory T cells) per individual, and 229 epigenome-wide DNA methylation profiles were generated using Illumina HumanMethylation450 BeadChips...
December 29, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/29285797/sodium-fluoride-disturbs-dna-methylation-of-nnat-and-declines-oocyte-quality-by-impairing-glucose-transport-in-porcine-oocytes
#8
Xiaoyan Liu, Zheng-Wen Nie, Ying-Ying Gao, Li Chen, Shu-Yuan Yin, Xia Zhang, Cuifang Hao, Yi-Liang Miao
Sodium fluoride (NaF) is used as a medicine to prevent tooth decay; however, excessive NaF could cause a pathological damage to the health. Recent studies showed that NaF impaired mouse oocyte maturation, included of abnormal spindle configuration, actin cap formation, cortical granule-free domain formation, and the following development after fertilization. However, few studies used large animals as models to study the toxicology of NaF on oocytes maturation. We proposed a hypothesis that NaF would affect the nuclear and cytoplasmic maturation of porcine oocytes and DNA methylation pattern of imprinted genes in oocytes...
December 29, 2017: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/29284398/mechanisms-of-radiation-bystander-and-non-targeted-effects-implications-to-radiation-carcinogenesis-and-radiotherapy
#9
Rasoul Yahyapour, Elahe Motevaseli, Abolhasan Rezaeyan, Hamid Abdollahi, Bagher Farhood, Mohsen Cheki, Masoud Najafi, Vilmar Villa
Knowledge of radiobiology is of paramount importance to be able to grasp and have an in-depth understanding of the consequences of ionizing radiation. One of the most important effects of this physical stressor's interaction to targeted and non-targeted cells, tissues and organs is on the late effects on the development of primary and secondary cancers. Thus, an in-depth understanding of the mechanisms of radiation carcinogenesis remain to be elucidated, and some studies have demonstrated or proposed a role of non-targeted effect in excess risk of cancer incidence...
December 29, 2017: Current Radiopharmaceuticals
https://www.readbyqxmd.com/read/29277783/up-regulation-of-uvrag-by-hdac1-inhibition-attenuates-5fu-induced-cell-death-in-hct116-colorectal-cancer-cells
#10
Yoon Kyung Jo, Na Yeon Park, Ji Hyun Shin, Doo Sin Jo, Ji-Eun Bae, Eun Sun Choi, Sungho Maeng, Hong Bae Jeon, Seon Ae Roh, Jong Wook Chang, Jin Cheon Kim, Dong-Hyung Cho
The ultraviolent irradiation resistance-associated gene (UVRAG), a component of the Beclin 1/autophagy-related 6 complex, regulates the autophagy initiation step and functions in the DNA-damage response. UVRAG is frequently mutated in various cancer types, and mutations of UVRAG increase sensitivity to chemotherapy by impairing DNA-damage repair. In this study, we addressed the epigenetic regulation of UVRAG in colorectal cancer cells. UVRAG expression was increased in cells treated with histone deacetylase (HDAC) inhibitors, such as valproic acid and suberoylanilide hydroxamic acid...
January 2018: Anticancer Research
https://www.readbyqxmd.com/read/29261844/crosstalk-between-histone-and-dna-methylation-in-regulation-of-retinal-matrix-metalloproteinase-9-in-diabetes
#11
Arul J Duraisamy, Manish Mishra, Renu A Kowluru
Purpose: Diabetes activates matrix metalloproteinase-9 (MMP-9), and MMP-9 via damaging retinal mitochondria, activates capillary cell apoptosis. MMP-9 promoter has binding sites for many transcription factors, and in diabetes its promoter undergoes epigenetic modifications, including histone modifications and DNA methylation. Enhancer of Zeste homolog 2 (Ezh2), which catalyzes dimethylation/trimethylation of histone 3 lysine 27 (H3K27me2 and me3), is also associated with DNA methylation...
December 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29244975/review-of-the-molecular-mechanisms-in-wound-healing-new-therapeutic-targets
#12
B Palmieri, M Vadalà, C Laurino
The restoration of the skin barrier in acute and chronic wounds is controlled by several molecular mechanisms that synergistically regulate cell kinetics, enzymatic functions, and neurovascular activation. These pathways include genetic and epigenetic activation, which modulate physiological wound healing. Our review describes the genetic background of skin repair, namely transcription-independent diffusible damage signals, individual variability, epigenetic mechanism, controlled qualitative traits, post-translational mechanisms, antioxidants, nutrients, DNA modifications, bacteria activation, mitochondrial activity, and oxidative stress...
December 2, 2017: Journal of Wound Care
https://www.readbyqxmd.com/read/29244183/dna-damage-and-epigenetic-alteration-in-soybean-farmers-exposed-to-complex-mixture-of-pesticides
#13
Danieli Benedetti, Barbara Lopes Alderete, Claudia Telles de Souza, Johnny Ferraz Dias, Liana Niekraszewicz, Mónica Cappetta, Wilner Martínez-López, Juliana Da Silva
Exposure to pesticides can trigger genotoxic and mutagenic processes through different pathways. However, epidemiological studies are scarce, and further work is needed to find biomarkers sensitive to the health of exposed populations. Considering that there are few evaluations of soybean farmers, the aim of this study was to assess the effects of human exposure to complex mixtures of pesticides. The alkaline comet assay modified with restriction enzyme (hOGG1: human 8-oxoguanine DNA glycosylase) was used to detect oxidised guanine, and compared with the buccal micronucleus cytome assay, global methylation, haematological parameters, biochemical analyses (serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, gamma-glutamyl-transferase and butyrylcholinesterase), and particle-induced X-ray emission (PIXE) for the analysis of inorganic elements...
December 13, 2017: Mutagenesis
https://www.readbyqxmd.com/read/29244109/gadd45a-promotes-active-dna-demethylation-of-the-mmp-9-promoter-via-base-excision-repair-pathway-in-ages-treated-keratinocytes-and-in-diabetic-male-rat-skin
#14
Liyan Zhou, Wei Wang, Chuan Yang, Tingting Zeng, Mengdie Hu, Xiaoyi Wang, Na Li, Kan Sun, Chuan Wang, Jing Zhou, Meng Ren, Li Yan
Diabetes elevates matrix metalloproteinase-9 (MMP-9) levels in the skin and its keratinocytes, and activated MMP-9 impairs skin wound healing. Epigenetic regulation of the DNA methylation status within the MMP-9 promoter plays an important role in the alteration of MMP-9 expression. Our aim was to investigate the role and mechanism of growth arrest and DNA damage-inducible 45a (GADD45a), a well-known DNA demethylation regulatory protein that mediates DNA methylation, in the regulation of MMP-9 expression. In this study, we showed that GADD45a was markedly upregulated in skin tissues from patients with diabetic foot ulcers, in diabetic rats and in human keratinocyte (HaCaT) cells exposed to advanced glycation end products (AGEs)...
December 13, 2017: Endocrinology
https://www.readbyqxmd.com/read/29242641/ubiquitin-ligases-in-oncogenic-transformation-and-cancer-therapy
#15
REVIEW
Daniela Senft, Jianfei Qi, Ze'ev A Ronai
The cellular response to external stress signals and DNA damage depends on the activity of ubiquitin ligases (E3s), which regulate numerous cellular processes, including homeostasis, metabolism and cell cycle progression. E3s recognize, interact with and ubiquitylate protein substrates in a temporally and spatially regulated manner. The topology of the ubiquitin chains dictates the fate of the substrates, marking them for recognition and degradation by the proteasome or altering their subcellular localization or assembly into functional complexes...
December 15, 2017: Nature Reviews. Cancer
https://www.readbyqxmd.com/read/29225734/pdrg1-at-the-interface-between-intermediary-metabolism-and-oncogenesis
#16
REVIEW
María Ángeles Pajares
PDRG1 is a small oncogenic protein of 133 residues. In normal human tissues, the p53 and DNA damage-regulated gene 1 (PDRG1) gene exhibits maximal expression in the testis and minimal levels in the liver. Increased expression has been detected in several tumor cells and in response to genotoxic stress. High-throughput studies identified the PDRG1 protein in a variety of macromolecular complexes involved in processes that are altered in cancer cells. For example, this oncogene has been found as part of the RNA polymerase II complex, the splicing machinery and nutrient sensing machinery, although its role in these complexes remains unclear...
November 26, 2017: World Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29212169/ccctc-binding-factor-inhibits-breast-cancer-cell-proliferation-and-metastasis-via-inactivation-of-the-nuclear-factor-kappab-pathway
#17
Jie Wu, Peng-Chang Li, Jun-Yi Pang, Guo-You Liu, Xue-Min Xie, Jia-Yao Li, Yi-Cong Yin, Jian-Hua Han, Xiu-Zhi Guo, Ling Qiu
CCCTC-binding factor (CTCF) is an important epigenetic regulator implicated in multiple cellular processes, including growth, proliferation, differentiation, and apoptosis. Although CTCF deletion or mutation has been associated with human breast cancer, the role of CTCF in breast cancer is questionable. We investigated the biological functions of CTCF in breast cancer and the underlying mechanism. The results showed that CTCF expression in human breast cancer cells and tissues was significantly lower than that in normal breast cells and tissues...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29206651/novel-therapeutic-strategies-and-targets-in-advanced-uveal-melanoma
#18
Vivian Chua, Andrew E Aplin
PURPOSE OF REVIEW: Currently, there are no U.S. Food and Drug Administration-approved or effective treatment options for advanced-stage uveal melanoma. In this article, we focus on therapeutic targets in pathways/mechanisms associated with common mutations in uveal melanoma. We review the challenges associated with targeting of these pathways and novel treatment strategies. RECENT FINDINGS: Common mutations that promote uveal melanoma initiation and progression include alterations in G protein subunit alpha q/11 (GNAQ/GNA11) and breast cancer gene 1-associated protein 1 (BAP1)...
December 4, 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/29199597/hepatocellular-carcinoma-and-possible-chemical-and-biological-causes-a-review
#19
Pinar Erkekoglu, Didem Oral, Ming-Wei Chao, Belmar Kocer-Gumusel
The development of hepatocellular carcinoma (HCC) is a multistep process. In HCC, progressive and morphologically distinct preneoplastic lesions/alterations associated with chronic liver injury, inflammation, hepatocellular degeneration/regeneration, necrosis, and small-cell dysplasia can be observed. The incidence of HCC exhibits regional and ethnic differences. Several cytotoxic and DNA-damaging chemicals are suggested to be the underlying causes of HCC-for example, acrylamide, perfluorooctanoic acid (PFOA), polychlorinated biphenyls (PCBs), benzo(a)pyrene (BaP), perfluorinated chemicals (PFCs), vinyl chloride monomer (VCM), and dietary contaminants (aflatoxins, ochratoxins)...
2017: Journal of Environmental Pathology, Toxicology and Oncology
https://www.readbyqxmd.com/read/29191063/changes-in-dna-methylation-induced-by-multi-walled-carbon-nanotube-exposure-in-the-workplace
#20
Manosij Ghosh, Deniz Öner, Katrien Poels, Ali M Tabish, Jelle Vlaanderen, Anjoeka Pronk, Eelco Kuijpers, Qing Lan, Roel Vermeulen, Bram Bekaert, Peter Hm Hoet, Lode Godderis
This study was designed to assess the epigenetic alterations in blood cells, induced by occupational exposure to multi-wall carbon nanotubes (MWCNT). The study population comprised of MWCNT-exposed workers (n=24) and unexposed controls (n=43) from the same workplace. We measured global DNA methylation/hydroxymethylation levels on the 5th cytosine residues using a validated liquid chromatography tandem-mass spectrometry (LC-MS/MS) method. Sequence-specific methylation of LINE1 retrotransposable element 1 (L1RE1) elements, and promoter regions of functionally important genes associated with epigenetic regulation [DNA methyltransferase-1 (DNMT1) and histone deacetylase 4 (HDAC4)], DNA damage/repair and cell cycle pathways [nuclear protein, coactivator of histone transcription/ATM serine/threonine kinase (NPAT/ATM)], and a potential transforming growth factor beta (TGF-β) repressor [SKI proto-oncogene (SKI)] were studied using bisulfite pyrosequencing...
November 30, 2017: Nanotoxicology
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