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https://www.readbyqxmd.com/read/29659445/ten-eleven-translocation-1-regulates-methylation-of-autophagy-related-genes-in-human-glioma
#1
Rui Fu, Yan Ding, Jie Luo, Kuan Ming Huang, Xiang Jun Tang, Dong Sheng Li, Shi Wen Guo
Ten-eleven translocation 1 catalyzes the conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), which plays an important role in epigenetics and is related to the malignant biological behavior of tumors. However, its regulatory role in glioma remains unclear. In this study, the levels of 5mC and 5hmC were detected using immunohistochemistry, dot-blot, hMeDIP-chip, and western blot in glioma tissues and normal brain tissues, whereas 5hmC differentially enriched genes were determined and further validated...
April 13, 2018: Neuroreport
https://www.readbyqxmd.com/read/29593282/vitamin-c-promotes-apoptosis-in-breast-cancer-cells-by-increasing-trail-expression
#2
David W Sant, Sushmita Mustafi, Christopher B Gustafson, Joshua Chen, Joyce M Slingerland, Gaofeng Wang
Genomic loss of 5-hydroxymethylcytosine (5hmC) accompanies malignant cellular transformation in breast cancer. Vitamin C serves as a cofactor for TET methylcytosine dioxygenases to increase 5hmC generation. Here we show that the transcription of SVCT2, a major vitamin C transporter, was decreased in human breast cancers (113 cases) compared to normal breast tissues from the same patients. A decreased SVCT2 expression was also observed in breast cancer cell lines. Treatment with vitamin C (100 μM) increased the 5hmC content in MDA-MB-231 breast cancer cells and markedly altered the transcriptome...
March 28, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29587824/distinctive-epigenomes-characterize-glioma-stem-cells-and-their-response-to-differentiation-cues
#3
Dan Zhou, Bonnie M Alver, Shuang Li, Ryan A Hlady, Joyce J Thompson, Mark A Schroeder, Jeong-Heon Lee, Jingxin Qiu, Philip H Schwartz, Jann N Sarkaria, Keith D Robertson
BACKGROUND: Glioma stem cells (GSCs) are a subpopulation of stem-like cells that contribute to glioblastoma (GBM) aggressiveness, recurrence, and resistance to radiation and chemotherapy. Therapeutically targeting the GSC population may improve patient survival, but unique vulnerabilities need to be identified. RESULTS: We isolate GSCs from well-characterized GBM patient-derived xenografts (PDX), characterize their stemness properties using immunofluorescence staining, profile their epigenome including 5mC, 5hmC, 5fC/5caC, and two enhancer marks, and define their transcriptome...
March 27, 2018: Genome Biology
https://www.readbyqxmd.com/read/29582271/reduced-hydroxymethylation-characterizes-medulloblastoma-while-tet-and-idh-genes-are-differentially-expressed-within-molecular-subgroups
#4
Karina Bezerra Salomão, Gustavo Alencastro Veiga Cruzeiro, Ricardo Bonfim-Silva, Lenisa Geron, Fernando Ramalho, Fabiano Pinto Saggioro, Luciano Neder Serafini, Daniel Antunes Moreno, Rosane Gomes de Paula Queiroz, Simone Dos Santos Aguiar, Izilda Cardinalli, José Andres Yunes, Silvia Regina Brandalise, Maria Sol Brassesco, Carlos Alberto Scrideli, Luiz Gonzaga Tone
INTRODUCTION: Medulloblastoma (MB) is an embryonal tumour that originates from genetic deregulation of cerebellar developmental pathways and is classified into 4 molecular subgroups: SHH, WNT, group 3, and group 4. Hydroxymethylation levels progressively increases during cerebellum development suggesting a possibility of deregulation in MB pathogenesis. The aim of this study was to investigate global hydroxymethylation levels and changes in TET and IDH gene expression in MB samples compared to control cerebellum samples...
March 26, 2018: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/29562912/gas5-is-an-essential-lncrna-regulator-for-self-renewal-and-pluripotency-of-mouse-embryonic-stem-cells-and-induced-pluripotent-stem-cells
#5
Jiajie Tu, Geng Tian, Hoi-Hung Cheung, Wei Wei, Tin-Lap Lee
BACKGROUND: The regulatory role of long noncoding RNAs (lncRNAs) have been partially proved in embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). METHODS: In the current study, we investigated mouse ESC (mESC) self-renewal, differentiation, and proliferation in vitro by knocking down a lncRNA, growth arrest specific 5 (Gas5). A series of related indicators were examined by cell counting kit-8 (CCK-8) assay, quantitative reverse-transcription polymerase chain reaction (qRT-PCR), Western blot, alkaline phosphatase staining, propidium iodide (PI) staining, Annexin V staining, competition growth assay, immunofluorescence, and chromatin immunoprecipitation (ChIP)-qPCR...
March 21, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29556496/tet-enzymes-variants-and-differential-effects-on-function
#6
REVIEW
Philippa Melamed, Yahav Yosefzon, Cfir David, Anna Tsukerman, Lilach Pnueli
Discovery of the ten-eleven translocation 1 (TET) methylcytosine dioxygenase family of enzymes, nearly 10 years ago, heralded a major breakthrough in understanding the epigenetic modifications of DNA. Initially described as catalyzing the oxidation of methyl cytosine (5mC) to hydroxymethyl cytosine (5hmC), it is now clear that these enzymes can also catalyze additional reactions leading to active DNA demethylation. The association of TET enzymes, as well as the 5hmC, with active regulatory regions of the genome has been studied extensively in embryonic stem cells, although these enzymes are expressed widely also in differentiated tissues...
2018: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/29518866/-the-effect-of-dna-hydroxymethylase-tet2-on-%C3%AE-globin-activation-in-the-treatment-of-%C3%AE-thalassemia
#7
W X Li, Q W Ma, F Y Zeng
Objective: To study the function of ten-eleven translocation 2 (Tet2) in γ globin gene expression in patients with β- thalassemia. Methods: Gamma globin expression was induced by 5-azacytidine and Tet2 gene expression was knocked down by short hairpin RNA (shRNA) in a human immortalized myelogenous leukemia K562 cell line. The global 5-hydroxymethylcytosine (5hmC) level was measured by an ELISA kit. 5hmC level of γ globin gene was quantified by sulfite sequencing. The mRNA level of Tet2, γ globin, and related transcription factors Nfe4 and Klf1 were quantified by real-time PCR...
March 1, 2018: Zhonghua Nei Ke za Zhi [Chinese Journal of Internal Medicine]
https://www.readbyqxmd.com/read/29503398/peroxiredoxin-as-a-functional-endogenous-antioxidant-enzyme-in-pronuclei-of-mouse-zygotes
#8
Kohtaro Morita, Mikiko Tokoro, Yuki Hatanaka, Chika Higuchi, Haruka Ikegami, Kouhei Nagai, Masayuki Anzai, Hiromi Kato, Tasuku Mitani, Yoshitomo Taguchi, Kazuo Yamagata, Yoshihiko Hosoi, Kei Miyamoto, Kazuya Matsumoto
Antioxidant mechanisms to adequately moderate levels of endogenous reactive oxygen species (ROS) are important for oocytes and embryos to obtain and maintain developmental competence, respectively. Immediately after fertilization, ROS levels in zygotes are elevated but the antioxidant mechanisms during the maternal-to-zygotic transition (MZT) are not well understood. First, we identified peroxiredoxin 1 (PRDX1) and PRDX2 by proteomics analysis as two of the most abundant endogenous antioxidant enzymes eliminating hydrogen peroxide (H2 O2 )...
March 2, 2018: Journal of Reproduction and Development
https://www.readbyqxmd.com/read/29489867/dynamics-of-male-canine-germ-cell-development
#9
Aline F de Souza, Naira C Godoy Pieri, Kelly C S Roballo, Fabiana F Bressan, Juliana B Casals, Carlos E Ambrósio, Felipe Perecin, Daniele S Martins
Primordial germ cells (PGCs) are precursors of gametes that can generate new individuals throughout life in both males and females. Additionally, PGCs have been shown to differentiate into embryonic germ cells (EGCs) after in vitro culture. Most studies investigating germinative cells have been performed in rodents and humans but not dogs (Canis lupus familiaris). Here, we elucidated the dynamics of the expression of pluripotent (POU5F1 and NANOG), germline (DDX4, DAZL and DPPA3), and epigenetic (5mC, 5hmC, H3K27me3 and H3K9me2) markers that are important for the development of male canine germ cells during the early (22-30 days post-fertilization (dpf)), middle (35-40 dpf) and late (45-50 dpf) gestational periods...
2018: PloS One
https://www.readbyqxmd.com/read/29483655/rna-dependent-chromatin-targeting-of-tet2-for-endogenous-retrovirus-control-in-pluripotent-stem-cells
#10
Diana Guallar, Xianju Bi, Jose Angel Pardavila, Xin Huang, Carmen Saenz, Xianle Shi, Hongwei Zhou, Francesco Faiola, Junjun Ding, Phensinee Haruehanroengra, Fan Yang, Dan Li, Carlos Sanchez-Priego, Arven Saunders, Feng Pan, Victor Julian Valdes, Kevin Kelley, Miguel G Blanco, Lingyi Chen, Huayan Wang, Jia Sheng, Mingjiang Xu, Miguel Fidalgo, Xiaohua Shen, Jianlong Wang
Ten-eleven translocation (TET) proteins play key roles in the regulation of DNA-methylation status by oxidizing 5-methylcytosine (5mC) to generate 5-hydroxymethylcytosine (5hmC), which can both serve as a stable epigenetic mark and participate in active demethylation. Unlike the other members of the TET family, TET2 does not contain a DNA-binding domain, and it remains unclear how it is recruited to chromatin. Here we show that TET2 is recruited by the RNA-binding protein Paraspeckle component 1 (PSPC1) through transcriptionally active loci, including endogenous retroviruses (ERVs) whose long terminal repeats (LTRs) have been co-opted by mammalian genomes as stage- and tissue-specific transcriptional regulatory modules...
March 2018: Nature Genetics
https://www.readbyqxmd.com/read/29482634/individual-retrotransposon-integrants-are-differentially-controlled-by-kzfp-kap1-dependent-histone-methylation-dna-methylation-and-tet-mediated-hydroxymethylation-in-na%C3%A3-ve-embryonic-stem-cells
#11
Andrea Coluccio, Gabriela Ecco, Julien Duc, Sandra Offner, Priscilla Turelli, Didier Trono
BACKGROUND: The KZFP/KAP1 (KRAB zinc finger proteins/KRAB-associated protein 1) system plays a central role in repressing transposable elements (TEs) and maintaining parent-of-origin DNA methylation at imprinting control regions (ICRs) during the wave of genome-wide reprogramming that precedes implantation. In naïve murine embryonic stem cells (mESCs), the genome is maintained highly hypomethylated by a combination of TET-mediated active demethylation and lack of de novo methylation, yet KAP1 is tethered by sequence-specific KZFPs to ICRs and TEs where it recruits histone and DNA methyltransferases to impose heterochromatin formation and DNA methylation...
February 26, 2018: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/29470917/theoretical-studies-on-the-photophysics-and-photochemistry-of-5-formylcytosine-and-5-carboxylcytosine-the-oxidative-products-of-epigenetic-modification-of-cytosine-in-dna
#12
Jinlu Xing, Yuejie Ai, Yang Liu, Jia Du, Weiqiang Chen, Zhanhui Lu, Xiangke Wang
Cytosine methylation and demethylation play crucial roles in understanding the genomic DNA expression regulation. The epigenetic modification of cytosine and its continuous oxidative products-the "new four bases of DNA" including 5-methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), 5-carboxylcytosine (5caC). However, compared to the abundant studies on the classical DNA bases, the photophysical and photochemical properties of those new bases have not yet aroused people's excessive attention...
February 22, 2018: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/29466726/tet2-rescues-age-related-regenerative-decline-and-enhances-cognitive-function-in-the-adult-mouse-brain
#13
Geraldine Gontier, Manasi Iyer, Jeremy M Shea, Gregor Bieri, Elizabeth G Wheatley, Miguel Ramalho-Santos, Saul A Villeda
Restoring adult stem cell function provides an exciting approach for rejuvenating the aging brain. However, molecular mechanisms mediating neurogenic rejuvenation remain elusive. Here we report that the enzyme ten eleven translocation methylcytosine dioxygenase 2 (Tet2), which catalyzes the production of 5-hydroxymethylcytosine (5hmC), rescues age-related decline in adult neurogenesis and enhances cognition in mice. We detected a decrease in Tet2 expression and 5hmC levels in the aged hippocampus associated with adult neurogenesis...
February 20, 2018: Cell Reports
https://www.readbyqxmd.com/read/29445086/the-oncogene-etv5-promotes-met-in-somatic-reprogramming-and-orchestrates-epiblast-primitive-endoderm-specification-during-mescs-differentiation
#14
Jinglong Zhang, Hongxia Cao, Jing Xie, Chen Fan, Youlong Xie, Xin He, Mingzhi Liao, Shiqiang Zhang, Huayan Wang
Unipotent spermatogonial stem cells (SSCs) can be efficiently reprogrammed into pluripotent stem cells only by manipulating the culture condition, without introducing exogenous reprogramming factors. This phenotype raises the hypothesis that the endogenous transcription factors (TFs) in SSCs may facilitate reprogramming to acquire pluripotency. In this study, we screened a pool of SSCs TFs (Bcl6b, Lhx1, Foxo1, Plzf, Id4, Taf4b, and Etv5), and found that oncogene Etv5 could dramatically increase the efficiency of induced pluripotent stem cells (iPSCs) generation when combined with Yamanaka factors...
February 14, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29432895/a-cross-omics-approach-to-investigate-temporal-gene-expression-regulation-by-5-hydroxymethylcytosine-via-tbh-derived-oxidative-stress-showed-involvement-of-different-regulatory-kinases
#15
Jacob J Briedé, Lize Deferme, Jarno E J Wolters, Sandra M H Claessen, Twan van den Beucken, J Richard Wagner, Simone G van Breda, Jos C S Kleinjans
Regulation of DNA methylation plays a crucial role in biological processes and carcinogenesis. The formation of 5-hydroxymethylcytosine (5hmC) by oxidation of 5-methylcytosine (5mC) has been proposed as an intermediate of active demethylation. However, whether and how active demethylation is regulated by oxidative stress-related processes is not well understood. Here we investigated whether free oxygen radicals are capable of directly forming 5hmC and how this enhanced whole genome gene expression. We applied LC-MS/MS technology for the analysis of 5mC, 5hmC, 5-formylcytosine (5fC) and 5-hydroxymethyluracyl (5hmU) in HepG2 cells exposed to hydroxyl- and methyl radicals, formed by tert-butyl hydroperoxide (TBH) at multiple time points...
February 9, 2018: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29430663/dna-hydroxymethylation-rate-in-the-ache-and-hoxc4-promoter-associated-with-human-sperm-quality
#16
Y Li, Y H Li, X Zhou, B Wu, J P Chen, Z K Wang, X Wang, H J Shi, R S Li
The relationship of altered DNA 5'-hydroxymethylation in human spermatozoa with seminal parameters remains unclear. The aim of the study was to investigate the association between the 5'-hydroxymethylcytosine (5hmC) rate in the promoters of acetylcholinesterase (AChE) and homeobox C4 (HoxC4) genes and human sperm concentration/motility. The study population consisted of three groups: asthenozoospermia (AZ), oligoasthenozoospermia (OAZ) and normozoospermia (NZ). The 5hmC rate in the promoter was measured by CCGG loci-dependent MspI/HpaII restriction mapping of glycosylation-modified sperm DNA combined with a hydroxymethylation-specific real-time polymerase chain reaction assay...
February 11, 2018: Andrologia
https://www.readbyqxmd.com/read/29428975/5-hydroxymethylcytosine-preferentially-targets-genes-upregulated-in-isocitrate-dehydrogenase-1-mutant-high-grade-glioma
#17
Wioletta K Glowacka, Harshika Jain, Makiko Okura, Abulizi Maimaitiming, Yasin Mamatjan, Romina Nejad, Hamza Farooq, Michael D Taylor, Kenneth Aldape, Paul Kongkham
Gliomas demonstrate epigenetic dysregulation exemplified by the Glioma CpG Island Methylator Phenotype (G-CIMP) seen in IDH1 mutant tumors. 5-Hydroxymethylcytosine (5hmC) is implicated in glioma pathogenesis; however, its role in IDH1 mutant gliomas is incompletely understood. To characterize 5hmC in IDH1 mutant gliomas further, we examine 5hmC in a cohort of IDH1 mutant and wild-type high-grade gliomas (HGG) using a quantitative locus-specific approach. Regions demonstrating high 5hmC abundance and differentially hydroxymethylated regions (DHMR) enrich for enhancers implicated in glioma pathogenesis...
February 10, 2018: Acta Neuropathologica
https://www.readbyqxmd.com/read/29422991/preeclampsia-is-associated-with-hypermethylation-of-igf-1-promoter-mediated-by-dnmt1
#18
Min Ma, Qiong-Jie Zhou, Yu Xiong, Bin Li, Xiao-Tian Li
Previous studies have demonstrated a dynamic epigenetic regulation of genes expression in placenta trophoblasts and a dynamic imbalance of DNA methylation and hydroxymethylation. Reduced IGF-1 has been observed in preeclampsia. This study was to investigate the interactive roles between IGF-1 and the global DNA methylation/hydroxymethylation, and the status of DNA methylation/hydroxymethylation and associated enzymes such as DNMTs and TETs in peeeclamptic placentas and hypoxic trophoblasts. It was found that IGF-1 was decreased in preeclamptic placentas and hypoxic trophoblasts when compared to the control group using immunohistochemisty, western blot, qRT-PCR and ELISA...
2018: American Journal of Translational Research
https://www.readbyqxmd.com/read/29411480/genome-re-sequencing-and-simple-sequence-repeat-markers-reveal-the-existence-of-divergent-lineages-in-the-canadian-puccinia-striiformis-f-sp-tritici-population-with-extensive-dna-methylation
#19
Gurcharn S Brar, Sajid Ali, Dinah Qutob, Stephen Ambrose, Kun Lou, Ron Maclachlan, Curtis J Pozniak, Yong-Bi Fu, Andrew G Sharpe, Hadley R Kutcher
Wheat stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), is an important disease in Canada. The worldwide genetic structure of Pst populations have been characterized, excluding Canada. Here, we elucidated the genetic structure of the western Canadian Pst population using molecular markers, revealing the presence of four divergent lineages with predominantly clonal structure. In the worldwide context, two previously reported lineages were identified: PstS0 (22%), representing an old northwestern-European, and PstS1 (35%), an invasive warm-temperature adapted...
February 6, 2018: Environmental Microbiology
https://www.readbyqxmd.com/read/29394393/decoding-the-dynamic-dna-methylation-and-hydroxymethylation-landscapes-in-endodermal-lineage-intermediates-during-pancreatic-differentiation-of-hesc
#20
Jia Li, Xinwei Wu, Yubin Zhou, Minjung Lee, Lei Guo, Wei Han, William Mo, Wen-Ming Cao, Deqiang Sun, Ruiyu Xie, Yun Huang
Dynamic changes in DNA methylation and demethylation reprogram transcriptional outputs to instruct lineage specification during development. Here, we applied an integrative epigenomic approach to unveil DNA (hydroxy)methylation dynamics representing major endodermal lineage intermediates during pancreatic differentiation of human embryonic stem cells (hESCs). We found that 5-hydroxymethylcytosine (5hmC) marks genomic regions to be demethylated in the descendent lineage, thus reshaping the DNA methylation landscapes during pancreatic lineage progression...
January 31, 2018: Nucleic Acids Research
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