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DNA demethylation

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https://www.readbyqxmd.com/read/29228771/curcumin-derivative-epigenetically-reactivates-nrf2-antioxidative-stress-signaling-in-mouse-prostate-cancer-tramp-c1-cells
#1
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/29228692/epigenetic-landscape-change-analysis-during-human-emt-sheds-light-on-a-key-emt-mediator-trim29
#2
Sung Kyung Choi, Kurinji Pandiyan, Jung Woo Eun, Xiaojing Yang, Seong Hwi Hong, Suk Woo Nam, Peter A Jones, Gangning Liang, Jueng Soo You
Epithelial to mesenchymal transition (EMT) is a key trans-differentiation process, which plays a critical role in physiology and pathology. Although gene expression changes in EMT have been scrutinized, study of epigenome is in its infancy. To understand epigenetic changes during TWIST-driven EMT, we used the AcceSssIble assay to study DNA methylation and chromatin accessibility in human mammary epithelial cells (HMECs). The DNA methylation changes were found to have functional significance in EMT - i.e. methylated genes were enriched for E-box motifs that can be recognized by TWIST, at the promoters suggesting a potential targeting phenomenon, whereas the demethylated regions were enriched for pro-metastatic genes, supporting the role of EMT in metastasis...
November 17, 2017: Oncotarget
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
#3
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/29224139/antibody-based-detection-of-global-nuclear-dna-methylation-in-cells-tissue-sections-and-mammalian-embryos
#4
Nathalie Beaujean, Juliette Salvaing, Nur Annies Abd Hadi, Sari Pennings
Immunostaining is widely used in cell biology for the in situ detection of proteins in fixed cells. The method is based on the specificity of antibodies for recognizing and binding to a selected target, combined with immunolabeling techniques for microscopic imaging. Antibodies with high specificities for modified nucleotides have also been widely developed, and among those, antibodies that recognize modified cytosine: 5-methylcytosine (5mC), and more recently, its derivates 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC)...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29224138/quantification-of-global-dna-methylation-levels-by-mass-spectrometry
#5
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
#6
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/29222117/pre-mrna-processing-includes-n6-methylation-of-adenosine-residues-that-are-retained-in-mrna-exons-and-the-fallacy-of-rna-epigenetics
#7
Robert B Darnell, Shengdong Ke, James E Darnell
By using a cell fraction technique that separates chromatin associated nascent RNA, newly completed nucleoplasmic mRNA and cytoplasmic mRNA, we have shown that residues in exons are methylated (m6A) in nascent pre-mRNA and remain methylated in the same exonic residues in nucleoplasmic and cytoplasmic mRNA. Thus, there is no evidence of a substantial degree of demethylation in mRNA exons that would correspond to so-called "epigenetic" demethylation. The turnover rate of mRNA molecules is faster depending on m6A content in HeLa cell mRNA suggesting specification of mRNA stability may be the major role of m6A exon modification...
December 8, 2017: RNA
https://www.readbyqxmd.com/read/29221486/a-screening-system-to-identify-transcription-factors-that-induce-binding-site-directed-dna-demethylation
#8
Takahiro Suzuki, Shiori Maeda, Erina Furuhata, Yuri Shimizu, Hajime Nishimura, Mami Kishima, Harukazu Suzuki
BACKGROUND: DNA methylation is a fundamental epigenetic modification that is involved in many biological systems such as differentiation and disease. We and others recently showed that some transcription factors (TFs) are involved in the site-specific determination of DNA demethylation in a binding site-directed manner, although the reports of such TFs are limited. RESULTS: Here, we develop a screening system to identify TFs that induce binding site-directed DNA methylation changes...
December 8, 2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/29221203/methylated-claudin-11-associated-with-metastasis-and-poor-survival-of-colorectal-cancer
#9
Jinyun Li, Chongchang Zhou, Shumin Ni, Shaomin Wang, Chao Ni, Ping Yang, Meng Ye
As one of crucial epigenetic modification, DNA methylation plays an important role during the carcinogenesis of colorectal cancer (CRC). In the current study, we used a human genome methylation array to detect the aberrant methylation genes in CRC. We further identified the hypermethylation of claudin-11 (CLDN11) and proved inverse correlation between CLDN11 methylation and its expression in CRC. In vitro experiments showed debased migration ability of colonic cancer cells in accompany with the converted methylation of CLDN11 after colonic cancer cells treated with demethylation agent, 5-aza-2'-deoxycytidine...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29212764/aberrant-dna-methylation-of-pregnane-x-receptor-underlies-metabolic-gene-alterations-in-the-diabetic-kidney
#10
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
https://www.readbyqxmd.com/read/29212263/combination-of-betulinic-acid-and-chidamide-inhibits-acute-myeloid-leukemia-by-suppression-of-the-hif1%C3%AE-pathway-and-generation-of-reactive-oxygen-species
#11
Hongyu Zhang, Ling Li, Min Li, Xiaodong Huang, Weiguo Xie, Wei Xiang, Paul Yao
Acute myeloid leukemia (AML) is a heterogeneous disorder of the hematopoietic system with no common genetic "Achilles heel" that can be targeted. Most patients respond well to standard therapy, while a majority relapse, and development of an effective therapy for AML patients is still urgently needed. In this study, we demonstrated that betulinic acid (BA) significantly increased Aryl hydrocarbon receptor (AHR) expression through demethylation on the AHR promoter in AML cells, and the increased AHR expression interacts with and sequesters ARNT, subsequently suppressing hypoxia-inducible factor-1α (HIF1α) pathway...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29209431/combining-cytogenetic-and-epigenetic-approaches-in-chronic-lymphocytic-leukemia-improves-prognosis-prediction-for-patients-with-isolated-13q-deletion
#12
Cristina Bagacean, Christelle Le Dantec, Christian Berthou, Adrian Tempescul, Hussam Saad, Anne Bordron, Mihnea Zdrenghea, Victor Cristea, Nathalie Douet-Guilbert, Yves Renaudineau
Background: Both defective DNA methylation and active DNA demethylation processes are emerging as important risk factors in chronic lymphocytic leukemia (CLL). However, associations between 5-cytosine epigenetic markers and the most frequent chromosomal abnormalities detected in CLL remain to be established. Methods: CLL patients were retrospectively classified into a cytogenetic low-risk group (isolated 13q deletion), an intermediate-risk group (normal karyotype or trisomy 12), and a high-risk group (11q deletion, 17p deletion, or complex karyotype [≥ 3 breakpoints])...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/29207640/accurate-quantification-of-5-methylcytosine-5-hydroxymethylcytosine-5-formylcytosine-and-5-carboxylcytosine-in-genomic-dna-from-breast-cancer-by-chemical-derivatization-coupled-with-ultra-performance-liquid-chromatography-electrospray-quadrupole-time-of-flight
#13
Mengzhe Guo, Xiao Li, Liyan Zhang, Dantong Liu, Wencheng Du, Dengyang Yin, Nan Lyu, Guangyu Zhao, Cheng Guo, Daoquan Tang
The DNA demethylation pathway has been discovered to play a significant role in DNA epigenetics. This pathway removes the methyl group from cytosine, which is involved in the oxidation of 5-methylcytosine to 5-hydroxymethylcytosine (5-hmC) by ten-eleven translocation (TET) proteins. Then, 5-hmC can be iteratively oxidized to generate 5-formylcytosine (5-foC) and 5-carboxylcytosine (5-caC). However, 5-hmC, 5-foC, and 5-caC are hardly detected due to their low content. In this study, we have developed a LC-HRMS method coupled with derivatization to accurately and simultaneously quantify 5-mC levels, along with its oxidation products in genomic DNA...
October 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/29204684/dna-methylation-of-the-cdc2l1-gene-promoter-region-decreases-the-expression-of-the-cdk11p58-protein-and-reduces-apoptosis-in-keloid-fibroblasts
#14
Gang Zhang, QiaoYu Guan, Guizong Chen, Fang Qian, Jie Liang
The excessive growth of fibroblasts in keloid is closely related to the status of gene methylation. The aim of this project was to study whether keloid development is related to DNA methylation in the CDC2L1 gene promoter region. DNA methylation of the promoter of this gene was analyzed by bisulfite sequencing and verified by DNA methylation-specific polymerase chain reaction. The results showed that the DNA methylation rate of CpG islands in the CDC2L1 gene promoter region was 50.0% (12/24) in patient keloid tissues and 0% (0/24) in normal skin-tissues from healthy controls...
December 4, 2017: Archives of Dermatological Research
https://www.readbyqxmd.com/read/29203910/tet-proteins-safeguard-bivalent-promoters-from-de-novo-methylation-in-human-embryonic-stem-cells
#15
Nipun Verma, Heng Pan, Louis C Doré, Abhijit Shukla, Qing V Li, Bobbie Pelham-Webb, Virginia Teijeiro, Federico González, Andrei Krivtsov, Chan-Jung Chang, Eirini P Papapetrou, Chuan He, Olivier Elemento, Danwei Huangfu
TET enzymes oxidize 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), which can lead to DNA demethylation. However, direct connections between TET-mediated DNA demethylation and transcriptional output are difficult to establish owing to challenges in distinguishing global versus locus-specific effects. Here we show that TET1, TET2 and TET3 triple-knockout (TKO) human embryonic stem cells (hESCs) exhibit prominent bivalent promoter hypermethylation without an overall corresponding decrease in gene expression in the undifferentiated state...
December 4, 2017: Nature Genetics
https://www.readbyqxmd.com/read/29203909/dynamic-epigenomic-landscapes-during-early-lineage-specification-in-mouse-embryos
#16
Yu Zhang, Yunlong Xiang, Qiangzong Yin, Zhenhai Du, Xu Peng, Qiujun Wang, Miguel Fidalgo, Weikun Xia, Yuanyuan Li, Zhen-Ao Zhao, Wenhao Zhang, Jing Ma, Feng Xu, Jianlong Wang, Lei Li, Wei Xie
In mammals, all somatic development originates from lineage segregation in early embryos. However, the dynamics of transcriptomes and epigenomes acting in concert with initial cell fate commitment remains poorly characterized. Here we report a comprehensive investigation of transcriptomes and base-resolution methylomes for early lineages in peri- and postimplantation mouse embryos. We found allele-specific and lineage-specific de novo methylation at CG and CH sites that led to differential methylation between embryonic and extraembryonic lineages at promoters of lineage regulators, gene bodies, and DNA-methylation valleys...
December 4, 2017: Nature Genetics
https://www.readbyqxmd.com/read/29203669/islet-cells-share-promoter-hypomethylation-independently-of-expression-but-exhibit-cell-type-specific-methylation-in-enhancers
#17
Daniel Neiman, Joshua Moss, Merav Hecht, Judith Magenheim, Sheina Piyanzin, A M James Shapiro, Eelco J P de Koning, Aharon Razin, Howard Cedar, Ruth Shemer, Yuval Dor
DNA methylation at promoters is an important determinant of gene expression. Earlier studies suggested that the insulin gene promoter is uniquely unmethylated in insulin-expressing pancreatic β-cells, providing a classic example of this paradigm. Here we show that islet cells expressing insulin, glucagon, or somatostatin share a lack of methylation at the promoters of the insulin and glucagon genes. This is achieved by rapid demethylation of the insulin and glucagon gene promoters during differentiation of Neurogenin3+ embryonic endocrine progenitors, regardless of the specific endocrine cell-type chosen...
December 4, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29203518/dna-methylation-in-epigenetic-inheritance-of-metabolic-diseases-through-the-male-germ-line
#18
Louise Rh Illum, Stine T Bak, Sten Lund, Anders Lade Nielsen
The global rise in metabolic diseases can be attributed to a complex interplay between biology, behavior and environmental factors. This article reviews the current literature concerning DNA methylation-based epigenetic inheritance (intergenerational and transgenerational) of metabolic diseases through the male germ line. Included are a presentation of the basic principles for DNA methylation in developmental programming, and a description of windows of susceptibility for the inheritance of environmentally induced aberrations in DNA methylation and their associated metabolic disease phenotypes...
December 4, 2017: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/29202805/clinical-significance-of-pcdh10-promoter-methylation-in-diffuse-large-b-cell-lymphoma
#19
Wenting Huang, Xuemin Xue, Ling Shan, Tian Qiu, Lei Guo, Jianming Ying, Ning Lu
BACKGROUND: PCDH10, one of the non-clustered protocadherins, is identified as a tumor suppressor gene in many tumors. Recently, promoter methylation of PCDH10 was found in diffuse large B-cell lymphoma (DLBCL) but not in normal lymph nodes, suggesting that its epigenetic aberrance is essential to the lymphomagenesis. However, there are few studies on the clinicopathological relevance and prognostic significance of PCDH10 methylation status in DLBCL. METHODS: One hundred-seven cases of DLBCL between Jan 2009 and Jul 2010 were selected to extract genomic DNA and perform bisulfite modification...
December 4, 2017: BMC Cancer
https://www.readbyqxmd.com/read/29199082/dact2-an-epigenetic-stimulator-exerts-dual-efficacy-for-colorectal-cancer-prevention-and-treatment
#20
Linlin Lu, Ying Wang, Rilan Ou, Qian Feng, Liyan Ji, Hongming Zheng, Yue Guo, Xiaoxiao Qi, Ah-Ng Tony Kong, Zhongqiu Liu
DACT2, a tumor suppressor gene in various tumors, is frequently down-regulated via hypermethylation. We found DACT2 gene expressions were dramatically silenced (P=0.002, n=8) in our clinical colorectal cancer (CRC) tissues, and TCGA data revealed DACT2 hypermethylation correlated to CRC poor prognosis (P=0.0129, HR=0.2153, n=248). Thus, by screening twelve nutritional compounds, we aim to find out an effective DACT2 epigenetic stimulator to determine whether DACT2 epigenetic restoration could reverse CRC tumorigenesis...
November 30, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
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