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DNA demethylation

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https://www.readbyqxmd.com/read/27917903/global-dna-methylation-variations-after-short-term-heat-shock-treatment-in-cultured-microspores-of-brassica-napus-cv-topas
#1
Jun Li, Qian Huang, Mengxiang Sun, Tianyao Zhang, Hao Li, Biyun Chen, Kun Xu, Guizhen Gao, Feng Li, Guixin Yan, Jiangwei Qiao, Yongping Cai, Xiaoming Wu
Heat stress can induce the cultured microspores into embryogenesis. In this study, whole genome bisulphite sequencing was employed to study global DNA methylation variations after short-term heat shock (STHS) treatments in cultured microspores of Brassica napus cv. Topas. Our results indicated that treatment on cultured Topas microspores at 32 °C for 6 h triggered DNA hypomethylation, particularly in the CG and CHG contexts. And the total number of T32 (Topas 32 °C for 6 h) vs. T0 (Topas 0 h) differentially methylated region-related genes (DRGs) was approximately two-fold higher than that of T18 (Topas 18 °C for 6 h) vs...
December 5, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27916785/the-differentially-dna-methylated-region-responsible-for-expression-of-runt-related-transcription-factor-2
#2
Shoichi Wakitani, Daigo Yokoi, Yuichi Hidaka, Koichiro Nishino
Runt-related transcription factor 2 (Runx2) is essential for osteogenesis. This study is aimed at identification of the genomic region differentially methylated in DNA for regulation of Runx2 expression. In the proximal promoter of mouse Runx2, DNA methylation was frequent at the region further than 3 kb relative to the transcription start site, in contrast to lower methylation status of the closer locus within 2 kb from the transcription start site. At the intermediate part, we identified a novel differentially methylated region in the Runx2 promoter region (Runx2-DMR): from -2...
December 4, 2016: Journal of Veterinary Medical Science
https://www.readbyqxmd.com/read/27916660/isoform-switch-of-tet1-regulates-dna-demethylation-and-mouse-development
#3
Wenhao Zhang, Weikun Xia, Qiujun Wang, Aaron J Towers, Jiayu Chen, Rui Gao, Yu Zhang, Chia-An Yen, Ah Young Lee, Yuanyuan Li, Chen Zhou, Kaili Liu, Jing Zhang, Tian-Peng Gu, Xiuqi Chen, Zai Chang, Danny Leung, Shaorong Gao, Yong-Hui Jiang, Wei Xie
The methylcytosine oxidase TET proteins play important roles in DNA demethylation and development. However, it remains elusive how exactly they target substrates and execute oxidation. Interestingly, we found that, in mice, the full-length TET1 isoform (TET1e) is restricted to early embryos, embryonic stem cells (ESCs), and primordial germ cells (PGCs). By contrast, a short isoform (TET1s) is preferentially expressed in somatic cells, which lacks the N terminus including the CXXC domain, a DNA-binding module that often recognizes CpG islands (CGIs) where TET1 predominantly occupies...
November 15, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27916276/a-surveillance-mechanism-ensures-repair-of-dna-lesions-during-zygotic-reprogramming
#4
Sabrina Ladstätter, Kikuë Tachibana-Konwalski
Sexual reproduction culminates in a totipotent zygote with the potential to produce a whole organism. Sperm chromatin reorganization and epigenetic reprogramming that alter DNA and histone modifications generate a totipotent embryo. Active DNA demethylation of the paternal genome has been proposed to involve base excision and DNA repair-based mechanisms. The nature and consequence of DNA lesions generated during reprogramming are not known. Using mouse genetics and chemical biology, we discovered that Tet3-dependent zygotic reprogramming generates paternal DNA lesions that are monitored by a surveillance mechanism...
November 21, 2016: Cell
https://www.readbyqxmd.com/read/27913994/sox2-inhibition-promotes-promoter-demethylation-of-cdx2-to-facilitate-gastric-intestinal-metaplasia
#5
Haijing Niu, Yuchen Jia, Tao Li, Bingzhong Su
BACKGROUND: Gastric intestinal metaplasia (IM) is regarded as a premalignant lesion, conferring risks for gastric cancer development. An intestinal transcription factor, CDX2, plays a vital role in establishing and maintaining IM. SOX2, an HMG-box transcription factor, is expressed in normal gastric mucosa and downregulated in IM. Therefore, it is important to elucidate the mutual interaction of SOX2 and CDX2 in gastric IM. AIMS: This study aims to evaluate the negative correlation between SOX2 and CDX2 in mRNA expression and promoter methylation and to illuminate the effect of SOX2 on the promoter methylation of CDX2...
December 2, 2016: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/27911980/cell-based-dna-demethylation-detection-system-for-screening-of-epigenetic-drugs-in-2d-3d-and-xenograft-models
#6
Khushboo Agrawal, Viswanath Das, Miroslav Otmar, Marcela Krečmerová, Petr Džubák, Marián Hajdúch
Aberrant DNA methylation that results in silencing of genes has remained a significant interest in cancer research. Despite major advances, the success of epigenetic therapy is elusive due to narrow therapeutic window. A wide variety of naturally occurring epigenetic agents and synthetic molecules that can alter methylation patterns exist, however, their usefulness in epigenetic therapy remains unknown. This underlines the need for effective tumor models for large-scale screening of drug candidates with potent hypomethylation activity...
December 2, 2016: Cytometry. Part A: the Journal of the International Society for Analytical Cytology
https://www.readbyqxmd.com/read/27911867/decreased-5-hydroxymethylcytosine-levels-correlate-with-cancer-progression-and-poor-survival-a-systematic-review-and-meta-analysis
#7
Zhaoli Chen, Xuejiao Shi, Lanwei Guo, Yuan Li, Mei Luo, Jie He
Ten-eleven translocation (TET) enzymes catalyze the oxidation of 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC) and then to 5-formylcytosine (5-fC) and 5-carboxylcytosine (5-caC), resulting in genomic DNA demethylation. Decreased 5-hmC levels have been reported in a variety of cancers, and loss of 5-hmC might be considered an epigenetic hallmark of cancer. However, the prognostic value of decreased 5-hmC in cancers remain controversial. Here, a systematic review was performed by conducting an electronic search of PubMed, EMBASE, Web of Science and the Cochrane Library...
November 30, 2016: Oncotarget
https://www.readbyqxmd.com/read/27905578/2-r-fluorinated-mc-hmc-fc-and-cac-triphosphates-are-substrates-for-dna-polymerases-and-tet-enzymes
#8
A S Schröder, E Parsa, K Iwan, F R Traube, M Wallner, S Serdjukow, T Carell
A deeper investigation of the chemistry that occurs on the newly discovered epigenetic DNA bases 5-hydroxymethyl-(hmdC), 5-formyl-(fdC), and 5-carboxy-deoxycytidine (cadC) requires chemical tool compounds, which are able to dissect the different potential reaction pathways in cells. Here we report that the 2'-(R)-fluorinated derivatives F-hmdC, F-fdC, and F-cadC, which are resistant to removal by base excision repair, are good substrates for DNA polymerases and TET enzymes. This result shows that the fluorinated compounds are ideal tool substances to investigate potential C-C-bond cleaving reactions in the context of active demethylation...
December 1, 2016: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/27904696/a-study-on-the-correlation-between-mthfr-promoter-methylation-and-diabetic-nephropathy
#9
Xiao-Hui Yang, Ren-Fang Cao, Yang Yu, Miao Sui, Tao Zhang, Jing-Yi Xu, Xiao-Mei Wang
OBJECTIVE: In order to observe the relationship between MTHFR promoter and DN, the determinations on MTHFR promoter methylation level and expression of HCY from DN patients have been carried out. METHODS: According to the Diabetes diagnosis and classification standard from WHO in 1999, 85 patients with DM diagnosed by Endocrinology and 30 healthy participants from our medical examination center were chosen as control specimen to study in this paper. All this specimen were divided into A, B, C and D four groups , which are corresponding simple diabetes mellitus group (SDM), early diabetic nephropathy group (EDN), clinical diabetic nephropathy group (CDN) and normal control group...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27902763/temperature-shift-alters-dna-methylation-and-histone-modification-patterns-in-gonadal-aromatase-cyp19a1-gene-in-species-with-temperature-dependent-sex-determination
#10
Yuiko Matsumoto, Brette Hannigan, David Crews
The environment surrounding the embryos has a profound impact on the developmental process and phenotypic outcomes of the organism. In species with temperature-dependent sex determination, gonadal sex is determined by the incubation temperature of the eggs. A mechanistic link between temperature and transcriptional regulation of developmental genes, however, remains elusive. In this study, we examine the changes in DNA methylation and histone modification patterns of the aromatase (cyp19a1) gene in embryonic gonads of red-eared slider turtles (Trachemys scripta) subjected to a temperature shift during development...
2016: PloS One
https://www.readbyqxmd.com/read/27893715/tgf%C3%AE-promotes-mesenchymal-phenotype-of-pancreatic-cancer-cells-in-part-through-epigenetic-activation-of-vav1
#11
P-H Huang, P-J Lu, L-Y Ding, P-C Chu, W-Y Hsu, C-S Chen, C-C Tsao, B-H Chen, C-T Lee, Y-S Shan, C-S Chen
The highly homeostasis-resistant nature of cancer cells leads to their escape from treatment and to liver metastasis, which in turn makes pancreatic ductal adenocarcinoma (PDAC) difficult to treat, especially the squamous/epithelial-to-mesenchymal transition (EMT)-like subtype. As the molecular mechanisms underlying tumour heterogeneity remain elusive, we investigated whether epigenetic regulation might explain inter-individual differences in the progression of specific subtypes. DNA methylation profiling performed on cancer tissues prior to chemo/radiotherapy identified one hypermethylated CpG site (CpG6882469) in the VAV1 gene body that was correlated with demethylation of two promoter CpGs (CpG6772370/CpG6772811) in both PDAC and peripheral blood...
November 28, 2016: Oncogene
https://www.readbyqxmd.com/read/27890639/oxidized-c5-methyl-cytosine-bases-in-dna-5-hydroxymethylcytosine-5-formylcytosine-and-5-carboxycytosine
#12
Arne Klungland, Adam B Robertson
Recent reports suggest that the Tet enzyme family catalytically oxidize 5-methylcytosine in mammalian cells. The oxidation of 5-methylcytosine can result in three chemically distinct species - 5-hydroxymethylcytsine, 5-formylcytosine, and 5-carboxycytosine. While the base excision repair machinery processes 5-formylcytosine and 5-carboxycytosine rapidly, 5-hydroxymethylcytosine is stable under physiological conditions. As a stable modification 5-hydroxymethylcytosine has a broad range of functions, from stem cell pluriopotency to tumorigenesis...
November 24, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27888420/endocan-as-a-prognostic-biomarker-of-triple-negative-breast-cancer
#13
Atsunobu Sagara, Katsuhide Igarashi, Maky Otsuka, Akihiro Kodama, Mutsumi Yamashita, Rei Sugiura, Takeshi Karasawa, Kazuhiko Arakawa, Michiko Narita, Naoko Kuzumaki, Minoru Narita, Yoshinori Kato
PURPOSE: Triple-negative breast cancer (TNBC) has aggressive characteristics and fewer treatment options than other subtypes. The purpose of this study was to explore prognostic biomarkers for TNBC that can be easily detected from the blood samples. METHODS: MDA-MB-231 and MDA-MB-231BR, a brain metastatic variant of the human TNBC cell line MDA-MB-231, were used as less and more aggressive models of TNBC, respectively. The extent to which the candidate gene/protein identified by RNA sequencing correlated well with aggressiveness of TNBC and how much protein was detected from the blood of tumor-bearing mice were evaluated...
November 25, 2016: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/27885421/role-of-vernalization-mediated-demethylation-in-the-floral-transition-of-brassica-rapa
#14
Weike Duan, Huijun Zhang, Bei Zhang, Xiaoting Wu, Shuaixu Shao, Ying Li, Xilin Hou, Tongkun Liu
Vernalization-mediated demethylation of BrCKA2 (casein kinase II α-subunit) and BrCKB4 (casein kinase II β-subunit) shorten the period of the clock gene BrCCA1 (circadian clock associated 1) in Brassica rapa. Photoperiod and vernalization are two environmental cues involved in the regulation of floral transition, but the ways in which they interact remain unclear. DNA methylation is one of the main mechanisms involved in controlling the functional state of chromatin and gene expression in response to environmental signals...
November 24, 2016: Planta
https://www.readbyqxmd.com/read/27880907/tet3-mediated-dna-demethylation-contributes-to-the-direct-conversion-of-fibroblast-to-functional-neuron
#15
Juan Zhang, Shuangquan Chen, Dongming Zhang, Zixiao Shi, Hong Li, Tongbiao Zhao, Baoyang Hu, Qi Zhou, Jianwei Jiao
The direct conversion of somatic cells to neurons by bypassing the multipotent cell state may be a powerful approach for personalized medicine. In addition to neuronal transcription factors and multiple small molecules, we find that epigenetic modification also contributes to the direct conversion of fibroblasts to neurons. Here, we show that Tet3, a DNA dioxygenase, can rapidly and efficiently convert fibroblasts directly into functional neurons. The induced neurons (iNs) express pan and mature neuronal markers such as Tuj1, Synapsin, and neuronal nuclei (NeuN)...
November 22, 2016: Cell Reports
https://www.readbyqxmd.com/read/27879253/the-yin-yang-dynamics-of-dna-methylation-is-the-key-regulator-for-smooth-muscle-cell-phenotype-switch-and-vascular-remodeling
#16
Jianhui Zhuang, Peipei Luan, Hailing Li, Kai Wang, Pei Zhang, Yawei Xu, Wenhui Peng
OBJECTIVE: DNA methylation plays an important role in chronic diseases such as atherosclerosis, yet the mechanisms are poorly understood. The objective of our study is to indicate the regulatory mechanisms of DNA methylation in vascular smooth muscle cells (VSMCs) and its roles in atherosclerosis. APPROACH AND RESULTS: In ApoE(-/-) mice fed a Western diet, DNA methyltransferase inhibitor, 5-aza-2'-deoxycytidine, significantly attenuated atherosclerotic lesions (20...
November 22, 2016: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/27877174/dna-methyltransferase-inhibitor-promotes-human-cd4-cd25-h-foxp3-regulatory-t-lymphocyte-induction-under-suboptimal-tcr-stimulation
#17
Chun-Hao Lu, Cheng-Jang Wu, Cheng-Chi Chan, Duc T Nguyen, Kuo-Ray Lin, Syh-Jae Lin, Li-Chen Chen, Jeffrey Jong-Yong Yen, Ming-Ling Kuo
The "master transcription factor" FOXP3 regulates the differentiation, homeostasis, and suppressor function of CD4(+) regulatory T (Treg) cells, which are critical in maintaining immune tolerance. Epigenetic regulation of FOXP3 expression has been demonstrated to be important to Treg cell development, but the induction of human Treg cells through epigenetic modification has not been clearly described. We report that the combination of the DNA methyltransferase inhibitor 5-azacytidine (5-Aza) and suboptimal T cell receptor (TCR) stimulation promoted CD4(+)CD25(h)FOXP3(+) T cell induction from human CD4(+)CD25(-) T cells...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27870873/herbivore-induced-dna-demethylation-changes-floral-signalling-and-attractiveness-to-pollinators-in-brassica-rapa
#18
Roman T Kellenberger, Philipp M Schlüter, Florian P Schiestl
Plants have to fine-tune their signals to optimise the trade-off between herbivore deterrence and pollinator attraction. An important mechanism in mediating plant-insect interactions is the regulation of gene expression via DNA methylation. However, the effect of herbivore-induced DNA methylation changes on pollinator-relevant plant signalling has not been systematically investigated. Here, we assessed the impact of foliar herbivory on DNA methylation and floral traits in the model crop plant Brassica rapa...
2016: PloS One
https://www.readbyqxmd.com/read/27869616/tet2-and-tet3-cooperate-with-b-lineage-transcription-factors-to-regulate-dna-modification-and-chromatin-accessibility
#19
Chan-Wang Lio, Jiayuan Zhang, Edahí González-Avalos, Patrick G Hogan, Xing Chang, Anjana Rao
Ten-eleven translocation (TET) enzymes oxidize 5-methylcytosine, facilitating DNA demethylation and generating new epigenetic marks. Here we show that concomitant loss of Tet2 and Tet3 in mice at early B cell stage blocked the pro- to pre-B cell transition in the bone marrow, decreased Irf4 expression and impaired the germline transcription and rearrangement of the Igκ locus. Tet2/3-deficient pro-B cells showed increased CpG methylation at the Igκ 3' and distal enhancers that was mimicked by depletion of E2A or PU...
November 21, 2016: ELife
https://www.readbyqxmd.com/read/27869171/epigenetic-activation-of-the-prostaglandin-receptor-ep4-promotes-resistance-to-endocrine-therapy-for-breast-cancer
#20
J F Hiken, J I McDonald, K F Decker, C Sanchez, J Hoog, N D VanderKraats, K L Jung, M Akinhanmi, L E Rois, M J Ellis, J R Edwards
Approximately 75% of breast cancers express estrogen receptor α (ERα) and depend on estrogen signals for continued growth. Aromatase inhibitors (AIs) prevent estrogen production and inhibit ER signaling, resulting in decreased cancer recurrence and mortality. Advanced tumors treated with AIs almost always develop resistance to these drugs via the upregulation of alternative growth signals. The mechanisms that drive this resistance-especially epigenetic events that alter gene expression-are, however, not well understood...
November 21, 2016: Oncogene
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