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active DNA demethylation

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https://www.readbyqxmd.com/read/29331774/the-synergy-of-vitamin-c-with-decitabine-activates-tet2-in-leukemic-cells-and-significantly-improves-overall-survival-in-elderly-patients-with-acute-myeloid-leukemia
#1
Huihui Zhao, Huayuan Zhu, Jiayu Huang, Yu Zhu, Ming Hong, Han Zhu, Jingjing Zhang, Shan Li, Lijia Yang, Yun Lian, Shuai Wang, Jianping Mao, Yaoyu Chen, Jianyong Li, Sixuan Qian
BACKGROUND: Decitabine is widely used in the treatment of acute myeloid leukemia (AML) in elderly patients. Low-dose Vitamin C has also been indicated to induce DNA demethylation at the cellular level. However, little is known whether low-dose Vitamin C has a synergistic effect with decitabine in clinic. METHODS: The effect of combined low-dose Vitamin C and decitabine on cell proliferation, the cell cycle, apoptosis and the expression level and activity of TET2 was investigated in HL60 and NB4 human leukemic cells...
January 2, 2018: Leukemia Research
https://www.readbyqxmd.com/read/29330295/epigenetic-reprogramming-of-pericentromeric-satellite-dna-in-premalignant-and-malignant-lesions
#2
Nadine H Brueckmann, Christina B Pedersen, Henrik J Ditzel, Morten F Gjerstorff
Repression of repetitive DNA is important for maintaining genomic stability, but is often perturbed in cancer. For instance, the megabase satellite domain at chromosome 1q12 is a common site of genetic rearrangements, such as translocations and deletions. Polycomb-group (PcG) proteins can be observed as large subnuclear domains called polycomb bodies, the composition and cellular function of which has remained elusive. This study, demonstrates that polycomb bodies are canonical subunits of the multiprotein polycomb repressive complex 1 (PRC1) deposited on 1q12 pericentromeric satellite DNA, which are normally maintained as constitutive heterochromatin by other mechanisms...
January 12, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29329300/symmetric-dimeric-bisbenzimidazoles-dbp-n-reduce-methylation-of-rarb-and-pten-while-significantly-increase-methylation-of-rrna-genes-in-mcf-7-cancer-cells
#3
Svetlana V Kostyuk, Margarita A Kvasha, Daria A Khrabrova, Olga V Kirsanova, Elizaveta S Ershova, Elena M Malinovskaya, Natalia N Veiko, Alexander A Ivanov, Vasiliy S Koval, Alexei L Zhuze, Vadim H Tashlitsky, Pavel E Umriukhin, Sergey I Kutsev, Elizaveta S Gromova
BACKGROUND: Hypermethylation is observed in the promoter regions of suppressor genes in the tumor cancer cells. Reactivation of these genes by demethylation of their promoters is a prospective strategy of the anticancer therapy. Previous experiments have shown that symmetric dimeric bisbenzimidazoles DBP(n) are able to block DNA methyltransferase activities. It was also found that DBP(n) produces a moderate effect on the activation of total gene expression in HeLa-TI population containing epigenetically repressed avian sarcoma genome...
2018: PloS One
https://www.readbyqxmd.com/read/29326044/escherichia-coli-single-stranded-dna-binding-protein-ssb-promotes-alkb-mediated-dna-dealkylation-repair
#4
Richa Nigam, Roy Anindya
Repair of alkylation damage in DNA is essential for maintaining genome integrity. Escherichia coli (E.coli) protein AlkB removes various alkyl DNA adducts including N1-methyladenine (N1meA) and N3-methylcytosine (N3meC) by oxidative demethylation. Previous studies showed that AlkB preferentially removes N1meA and N3meC from single-stranded DNA (ssDNA). It can also remove N1meA and N3meC from double-stranded DNA by base-flipping. Notably, ssDNA produced during DNA replication and recombination, remains bound to E...
January 8, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29318497/epigenetic-mechanism-of-survivin-dysregulation-in-human-cancer
#5
REVIEW
Hui Lyu, Jingcao Huang, Zhimin He, Bolin Liu
Survivin (coding gene BIRC5) is a dual functional protein acting as a critical inhibitor of apoptosis (IAP) and key regulator of cell cycle progression. It is usually produced in embryonic tissues during development and undetectable in most adult tissues. Overexpression of Survivin frequently occurs in various human cancers and increased Survivin correlates with poor clinic outcome, tumor recurrence, and therapeutic resistance. Because of its selective expression in tumor, but not normal tissues, Survivin has been recognized as an attractive target for cancer treatment...
January 4, 2018: Science China. Life Sciences
https://www.readbyqxmd.com/read/29296817/runx1-regulates-site-specificity-of-dna-demethylation-by-recruitment-of-dna-demethylation-machineries-in-hematopoietic-cells
#6
Takahiro Suzuki, Yuri Shimizu, Erina Furuhata, Shiori Maeda, Mami Kishima, Hajime Nishimura, Saaya Enomoto, Yoshihide Hayashizaki, Harukazu Suzuki
RUNX1 is an essential master transcription factor in hematopoietic development and plays important roles in immune functions. Although the gene regulatory mechanism of RUNX1 has been characterized extensively, the epigenetic role of RUNX1 remains unclear. Here, we demonstrate that RUNX1 contributes DNA demethylation in a binding site-directed manner in human hematopoietic cells. Overexpression analysis of RUNX1 showed the RUNX1-binding site-directed DNA demethylation. The RUNX1-mediated DNA demethylation was also observed in DNA replication-arrested cells, suggesting an involvement of active demethylation mechanism...
September 12, 2017: Blood Advances
https://www.readbyqxmd.com/read/29281729/histone-demethylase-lsd1-restricts-influenza-a-virus-infection-by-erasing-ifitm3-k88-monomethylation
#7
Jiaoyu Shan, Binbin Zhao, Zhao Shan, Jia Nie, Rong Deng, Rui Xiong, Andy Tsun, Weiqi Pan, Hanzhi Zhao, Ling Chen, Ying Jin, Zhikang Qian, Kawing Lui, Rui Liang, Dan Li, Bing Sun, Dimitri Lavillette, Ke Xu, Bin Li
The histone demethylase LSD1 has been known as a key transcriptional coactivator for DNA viruses such as herpes virus. Inhibition of LSD1 was found to block viral genome transcription and lytic replication of DNA viruses. However, RNA virus genomes do not rely on chromatin structure and histone association, and the role of demethylase activity of LSD1 in RNA virus infections is not anticipated. Here, we identify that, contrary to its role in enhancing DNA virus replication, LSD1 limits RNA virus replication by demethylating and activating IFITM3 which is a host restriction factor for many RNA viruses...
December 27, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/29277934/fam20c-could-be-targeted-by-tet1-to-promote-odontoblastic-differentiation-potential-of-human-dental-pulp-cells
#8
Qimeng Li, Baicheng Yi, Zhihui Feng, Runsha Meng, Cheng Tian, Qiong Xu
OBJECTIVES: Ten-eleven translocation 1 (TET1) is a DNA methylcytosine (mC) dioxygenase discovered recently that can convert 5-mC into 5-hydroxymethylcytosine (5hmC). We previously reported that TET1 promotes odontoblastic differentiation of human dental pulp cells (hDPCs). The gene encoding the family with sequence similarity 20, member C (FAM20C) protein, is a potential TET1 target and showed demethylation during odontoblastic differentiation of hDPCs in our previous study. This study aimed to explore whether TET1-mediated hydroxymethylation could activate the FAM20C gene, thereby regulating hDPC differentiation...
December 25, 2017: Cell Proliferation
https://www.readbyqxmd.com/read/29275584/-dna-methylation-modification-of-brms1-in-triple-negative-breast-cancer-and-its-correlation-with-tumor-metastasis
#9
J Xia, Z D Lü, P H Zhou, S C Cui, B Kong, D Liu, S S Long, X H Zhang, J J Zhao
Objective: To investigate the effect of methylation status of breast cancer metastasis suppressor gene 1 (BRMS1) on the expression of breast cancer and the biological behavior of cancer cells in triple-negative breast cancer (TNBC). Methods: The expression of BRMS1 in TNBC tissues and corresponding non-malignant tissues and its relationship with clinicopathological parameters were detected by immunohistochemistry. The mRNA and protein expression of BRMS1 in normal breast epithelial cells and TNBC cells were detected by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting...
November 28, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/29248296/synthesis-and-biological-evaluation-of-4%C3%AE-thiazol-2-yl-amino-4-o-demethyl-4-deoxypodophyllotoxins-as-topoisomerase-ii-inhibitors
#10
Chun-Yan Sang, Heng-Zhi Tian, Yue Chen, Jian-Fei Liu, Shi-Wu Chen, Ling Hui
A series of 4β-(thiazol-2-yl)amino-4'-O-demethyl-4-deoxypodophyllotoxins were synthesized, and their cytotoxicities were evaluated against four human cancer cell lines (A549, HepG2, HeLa, and LOVO cells) and normal human diploid fibroblast line WI-38. Some of the compounds exhibited promising antitumor activity and less toxicity than the anticancer drug etoposide. Among them, compounds 15 and 17 were found to be the most potent synthetic derivatives as topo-II inhibitors, and induced DNA double-strand breaks via the p73/ATM pathway as well as the H2AX phosphorylation in A549 cells...
December 7, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29246089/expression-and-regulation-of-retinoic-acid-receptor-responders-in-the-human-placenta
#11
Hanna Huebner, Andrea Hartner, Wolfgang Rascher, Reiner Strick R, Sven Kehl, Felix Heindl, David L Wachter, Matthias W Beckmann, Fabian B Fahlbusch, Matthias Ruebner
INTRODUCTION: Retinoic acid (RA) signaling through its receptors (RARA, RARB, RARG, and the retinoic X receptor RXRA) is essential for healthy placental and fetal development. An important group of genes regulated by RA are the RA receptor responders (RARRES1, 2, and 3). We set out to analyze their expression and regulation in healthy and pathologically altered placentas of preeclampsia (PE) and intrauterine growth restriction (IUGR) as well as in trophoblast cell lines. METHODS: We performed immunohistochemical staining on placental sections and analyzed gene expression by real-time polymerase chain reaction...
January 1, 2017: Reproductive Sciences
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
#12
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/29242626/stable-transgenerational-epigenetic-inheritance-requires-a-dna-methylation-sensing-circuit
#13
Ben P Williams, Mary Gehring
Epigenetic states are stably propagated in eukaryotes. In plants, DNA methylation patterns are faithfully inherited over many generations but it is unknown how the dynamic activities of cytosine DNA methyltransferases and 5-methylcytosine DNA glycosylases interact to maintain epigenetic homeostasis. Here we show that a methylation-sensing gene regulatory circuit centered on a 5-methylcytosine DNA glycosylase gene is required for long-term epigenetic fidelity in Arabidopsis. Disrupting this circuit causes widespread methylation losses and abnormal phenotypes that progressively worsen over generations...
December 14, 2017: Nature Communications
https://www.readbyqxmd.com/read/29242529/decitabine-a-dna-demethylating-agent-promotes-differentiation-via-notch1-signaling-and-alters-immune-related-pathways-in-muscle-invasive-bladder-cancer
#14
Swathi Ramakrishnan, Qiang Hu, Nithya Krishnan, Dan Wang, Evelyn Smit, Victoria Granger, Monika Rak, Kristopher Attwood, Candace Johnson, Carl Morrison, Roberto Pili, Gurkamal Chatta, Khurshid Guru, Geraldine Gueron, Lacey McNally, Jianmin Wang, Anna Woloszynska-Read
Aberrant DNA methylation observed in cancer can provide survival benefits to cells by silencing genes essential for anti-tumor activity. DNA-demethylating agents such as Decitabine (DAC)/Azacitidine (AZA) activate otherwise silenced tumor suppressor genes, alter immune response and epigenetically reprogram tumor cells. In this study, we show that non-cytotoxic nanomolar DAC concentrations modify the bladder cancer transcriptome to activate NOTCH1 at the mRNA and protein level, increase double-stranded RNA sensors and CK5-dependent differentiation...
December 14, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29235922/dna-methylation-reprogramming-of-human-cancer-cells-by-expression-of-a-plant-5-methylcytosine-dna-glycosylase
#15
Teresa Morales-Ruiz, María Victoria García-Ortiz, Iván Devesa-Guerra, Laura Raya-Ruiz, Juan R Tejedor, Gustavo F Bayón, Marta I Sierra, Mario F Fraga, Rafael R Ariza, Teresa Roldán-Arjona
Patterns of DNA methylation, an important epigenetic modification involved in gene silencing and development, are disrupted in cancer cells. Understanding the functional significance of aberrant methylation in tumors remains challenging, due in part to the lack of suitable tools to actively modify methylation patterns. DNA demethylation caused by mammalian DNA methyltransferase inhibitors is transient and replication-dependent, whereas that induced by TET enzymes involves oxidized 5mC derivatives that perform poorly understood regulatory functions...
December 13, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/29228771/curcumin-derivative-epigenetically-reactivates-nrf2-antioxidative-stress-signaling-in-mouse-prostate-cancer-tramp-c1-cells
#16
Wenji Li, Zheng-Yuan Su, Yue Guo, Chengyue Zhang, RenYi Wu, Linbo Gao, Xi Zheng, Zhi-Yun Du, Kun Zhang, Ah-Ng Kong
The carcinogenesis of prostate cancer (PCa) in TRAMP model is highly correlated with hypermethylation in the promoter region of Nrf2 and the accompanying reduced transcription of Nrf2 and its regulated detoxifying genes. We aimed to investigate the effects of (3E,5E)-3,5-Bis(3,4,5-trimethoxybenzylidene) -tetrahydrothiopyran-4-one (F10) and (3E,5E)-3,5-Bis(3,4,5-trimethoxybenzylidene) -tetrahydropyran-4-one (E10), two synthetic curcumin derivatives, on restoring Nrf2 activity in TRAMP C1 cells. HepG2-C8 cells transfected with an antioxidant-response element (ARE)-luciferase vector were treated with F10, E10, curcumin and sulforaphane (SFN) to compare their effects on Nrf2-ARE pathways...
December 11, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/29228451/rg108-induces-the-apoptosis-of-endometrial-cancer-ishikawa-cell-lines-by-inhibiting-the-expression-of-dnmt3b-and-demethylation-of-hmlh1
#17
L Yang, J Hou, X-H Cui, L-N Suo, Y-W Lv
OBJECTIVE: The effects of DNA methyltransferase (DNMT) inhibitor RG108 on the proliferation and apoptosis of endometrial cancer was investigated, and whether its mechanism was related to the inhibition of DNMT3B, thereby affecting the human mutL homolog 1 (hMLH1) methylation status and its expression, was further studied. MATERIALS AND METHODS: Culture of human endometrial cancer Ishikawa cell lines: cells grew adhering to the wall in Roswell Park Memorial Institute-1640 (RPMI-1640) medium (supplemented with 10% fetal bovine serum (FBS) and 2 mM L-glutamic acid)...
November 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29224138/quantification-of-global-dna-methylation-levels-by-mass-spectrometry
#18
Agustin F Fernandez, Luis Valledor, Fernando Vallejo, Maria Jesús Cañal, Mario F Fraga
Global DNA methylation was classically considered the relative percentage of 5-methylcysine (5mC) with respect to total cytosine (C). Early approaches were based on the use of high-performance separation technologies and UV detection. However, the recent development of protocols using mass spectrometry for the detection has increased sensibility and permitted the precise identification of peak compounds based on their molecular masses. This allows work to be conducted with much less genomic DNA starting material and also to quantify 5-hydroxymethyl-cytosine (5hmC), a recently identified form of methylated cytosine that could play an important role in active DNA demethylation...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29223816/cortex-and-hippocampus-dna-epigenetic-response-to-a-long-term-arsenic-exposure-via-drinking-water
#19
Xiaoyan Du, Meiping Tian, Xiaoxue Wang, Jie Zhang, Qingyu Huang, Liangpo Liu, Heqing Shen
The neurotoxicity of arsenic is a serious health problem, especially for children. DNA epigenetic change may be an important pathogenic mechanism, but the molecular pathway remains obscure. In this study, the weaned male Sprague-Dawly (SD) rats were treated with arsenic trioxide via drinking water for 6 months, simulating real developmental exposure situation of children. Arsenic exposure impaired the cognitive abilities, and altered the expression of neuronal activity-regulated genes. Total arsenic concentrations of cortex and hippocampus tissues were significantly increased in a dose-dependent manner...
December 7, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/29212764/aberrant-dna-methylation-of-pregnane-x-receptor-underlies-metabolic-gene-alterations-in-the-diabetic-kidney
#20
Atsushi Watanabe, Takeshi Marumo, Wakako Kawarazaki, Mitsuhiro Nishimoto, Nobuhiro Ayuzawa, Kohei Ueda, Daigoro Hirohama, Toshiya Tanaka, Shintaro Yagi, Satoshi Ota, Genta Nagae, Hiroyuki Aburatani, Hiroo Kumagai, Toshiro Fujita
Epigenetic abnormalities have been suggested to mediate metabolic memory observed in diabetic complications. We have shown that epigenetic alterations may induce persistent phenotypic changes in the proximal tubules of the diabetic kidneys. In this study, we show that pregnane X receptor (PXR), a xenobiotic nuclear receptor, is epigenetically altered and upregulated, and may have a possible function in the diabetic kidney. PXR has been shown to play a critical role in metabolic changes in obesity and diabetes; however, its distribution and function in the kidney are unknown...
December 6, 2017: American Journal of Physiology. Renal Physiology
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