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https://www.readbyqxmd.com/read/29772801/ogt-o-glcnac-transferase-selectively-modifies-multiple-residues-unique-to-lamin-a
#1
Dan N Simon, Amanda Wriston, Qiong Fan, Jeffrey Shabanowitz, Alyssa Florwick, Tejas Dharmaraj, Sherket B Peterson, Yosef Gruenbaum, Cathrine R Carlson, Line M Grønning-Wang, Donald F Hunt, Katherine L Wilson
The LMNA gene encodes lamins A and C with key roles in nuclear structure, signaling, gene regulation, and genome integrity. Mutations in LMNA cause over 12 diseases ('laminopathies'). Lamins A and C are identical for their first 566 residues. However, they form separate filaments in vivo, with apparently distinct roles. We report that lamin A is β- O -linked N -acetylglucosamine- (O -GlcNAc)-modified in human hepatoma (Huh7) cells and in mouse liver. In vitro assays with purified O -GlcNAc transferase (OGT) enzyme showed robust O -GlcNAcylation of recombinant mature lamin A tails (residues 385⁻646), with no detectable modification of lamin B1, lamin C, or 'progerin' (Δ50) tails...
May 17, 2018: Cells
https://www.readbyqxmd.com/read/29768411/cytoskeleton-structure-and-total-methylation-of-mouse-cardiac-and-lung-tissue-during-space-flight
#2
Irina V Ogneva, Sergey S Loktev, Vladimir N Sychev
The purpose of this work was to evaluate the protein and mRNA expression levels of multiple cytoskeletal proteins in the cardiac and lung tissue of mice that were euthanized onboard the United States Orbital Segment of the International Space Station 37 days after the start of the SpaceX-4 mission (September 2014, USA). The results showed no changes in the cytoskeletal protein content in the cardiac and lung tissue of the mice, but there were significant changes in the mRNA expression levels of the associated genes, which may be due to an increase in total genome methylation...
2018: PloS One
https://www.readbyqxmd.com/read/29757674/eicosapentaenoic-acid-induces-dna-demethylation-in-carcinoma-cells-through-a-tet1-dependent-mechanism
#3
Veronica Ceccarelli, Virginia Valentini, Simona Ronchetti, Lorenza Cannarile, Monia Billi, Carlo Riccardi, Laura Ottini, Vincenzo Nicola Talesa, Francesco Grignani, Alba Vecchini
In cancer cells, global genomic hypomethylation is found together with localized hypermethylation of CpG islands within the promoters and regulatory regions of silenced tumor suppressor genes. Demethylating agents may reverse hypermethylation, thus promoting gene re-expression. Unfortunately, demethylating strategies are not efficient in solid tumor cells. DNA demethylation is mediated by ten-eleven translocation enzymes (TETs). They sequentially convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), which is associated with active transcription; 5-formylcytosine; and finally, 5-carboxylcytosine...
May 14, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29733394/sin3a-tet1-interaction-activates-gene-transcription-and-is-required-for-embryonic-stem-cell-pluripotency
#4
Fugui Zhu, Qianshu Zhu, Dan Ye, Qingquan Zhang, Yiwei Yang, Xudong Guo, Zhenping Liu, Zeyidan Jiapaer, Xiaoping Wan, Guiying Wang, Wen Chen, Songcheng Zhu, Cizhong Jiang, Weiyang Shi, Jiuhong Kang
Sin3a is a core component of histone-deacetylation-activity-associated transcriptional repressor complex, playing important roles in early embryo development. Here, we reported that down-regulation of Sin3a led to the loss of embryonic stem cell (ESC) self-renewal and skewed differentiation into mesendoderm lineage. We found that Sin3a functioned as a transcriptional coactivator of the critical Nodal antagonist Lefty1 through interacting with Tet1 to de-methylate the Lefty1 promoter. Further studies showed that two amino acid residues (Phe147, Phe182) in the PAH1 domain of Sin3a are essential for Sin3a-Tet1 interaction and its activity in regulating pluripotency...
May 4, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29732371/hippocampal-tet1-and-tet2-expression-and-dna-hydroxymethylation-are-affected-by-physical-exercise-in-aged-mice
#5
Peter Jessop, Maria Toledo-Rodriguez
The function of 5-hydroxymethylcytosine (5hmC) is poorly understood. 5hmC is an epigenetic modification of DNA, resulting from the oxidation of 5-methylcytosine (5mC) by the Fe2+ , and 2-oxoglutarate-dependent, 10-11 translocation methylcytosine dioxygenases (TET1, TET2, and TET3). Recent evidence suggests that, in addition to being an intermediate in active demethylation, 5hmC may also have an epigenetic role. 5hmC is enriched in the adult brain, where it has been implicated in regulating neurogenesis. The rate of adult neurogenesis decreases with age, however physical exercise has been shown to counteract this deficit...
2018: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/29715584/duox2-mediated-production-of-reactive-oxygen-species-induces-epithelial-mesenchymal-transition-in-5-fluorouracil-resistant-human-colon-cancer-cells
#6
Kyoung Ah Kang, Yea Seong Ryu, Mei Jing Piao, Kristina Shilnikova, Hee Kyoung Kang, Joo Mi Yi, Mathias Boulanger, Rosa Paolillo, Guillaume Bossis, Sung Young Yoon, Seong Bong Kim, Jin Won Hyun
The therapeutic benefits offered by 5-fluorouracil (5-FU) are limited because of the acquisition of drug resistance, the main cause of treatment failure and metastasis. The ability of the cancer cells to undergo epithelial-mesenchymal transition (EMT) contributes significantly to cancer metastatic potential and chemo-resistance. However, the underlying molecular mechanisms of 5-FU-resistance have remained elusive. Here, we show that reactive oxygen species (ROS), produced by dual oxidase 2 (DUOX2), promote 5-FU-induced EMT...
April 23, 2018: Redox Biology
https://www.readbyqxmd.com/read/29679667/systemic-delivery-of-bace1-sirna-through-neuron-targeted-nanocomplexes-for-treatment-of-alzheimer-s-disease
#7
Pengzhen Wang, Xiaoyao Zheng, Qian Guo, Peng Yang, Xiaoying Pang, Kang Qian, Wei Lu, Qizhi Zhang, Xinguo Jiang
β-site amyloid precursor protein cleaving enzyme 1 (BACE1) is a key enzyme to cleave the amyloid precursor protein to develop Alzheimer's disease (AD). Reducing BACE1 expression in central neuron through RNA interference technology shows great promise to overcome AD. However, to obtain an efficient and neurons-specific delivery of siRNA against BACE1 through systemic administration remains challenging. Here, we design and prepare siRNA nano-carriers based on PEGylated poly(2-(N,N-dimethylamino) ethyl methacrylate) (PEG-PDMAEMA) modified with both the CGN peptide for blood-brain barrier (BBB) penetration and the Tet1 peptide for neuron-specific binding...
April 18, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29665328/effects-of-exposure-to-acetaminophen-and-ibuprofen-on-fetal-germ-cell-development-in-both-sexes-in-rodent-and-human-using-multiple-experimental-systems
#8
Pablo Hurtado-Gonzalez, Richard A Anderson, Joni Macdonald, Sander van den Driesche, Karen Kilcoyne, Anne Jørgensen, Chris McKinnell, Sheila Macpherson, Richard M Sharpe, Rod T Mitchell
BACKGROUND: Analgesic exposure during pregnancy may affect aspects of fetal gonadal development that are targeted by endocrine disruptors. OBJECTIVES: We investigated whether therapeutically relevant doses of acetaminophen and ibuprofen affect germ cell (GC) development in human fetal testes/ovaries using in vitro and xenograft approaches. METHODS: First-trimester human fetal testes/ovaries were cultured and exposed to acetaminophen or ibuprofen (7 d)...
April 16, 2018: Environmental Health Perspectives
https://www.readbyqxmd.com/read/29665240/thioether-macrocyclic-peptides-selected-against-tet1-compact-catalytic-domain-inhibit-tet1-catalytic-activity
#9
Kosuke Nishio, Roman Belle, Takayuki Katoh, Akane Kawamura, Toru Sengoku, Kazuharu Hanada, Noboru Ohsawa, Mikako Shirouzu, Shigeyuki Yokoyama, Hiroaki Suga
The ten-eleven translocation (TET) protein family, consisting of three isoforms (TET1/2/3), have been found in mammalian cells and have a crucial role in 5-methycytosine demethylation in genomic DNA through the catalysis of oxidation reactions assisted by 2-oxoglutarate (2OG). DNA methylation/demethylation contributes to the regulation of gene expression at the transcriptional level, and recent studies have revealed that TET1 is highly elevated in malignant cells of various diseases and related to malignant alteration...
April 17, 2018: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/29662175/pluripotency-transcription-factors-and-tet1-2-maintain-brd4-independent-stem-cell-identity
#10
Lydia W S Finley, Santosha A Vardhana, Bryce W Carey, Direna Alonso-Curbelo, Richard Koche, Yanyang Chen, Duancheng Wen, Bryan King, Megan R Radler, Shahin Rafii, Scott W Lowe, C David Allis, Craig B Thompson
A robust network of transcription factors and an open chromatin landscape are hallmarks of the naive pluripotent state. Recently, the acetyllysine reader Brd4 has been implicated in stem cell maintenance, but the relative contribution of Brd4 to pluripotency remains unclear. Here, we show that Brd4 is dispensable for self-renewal and pluripotency of embryonic stem cells (ESCs). When maintained in their ground state, ESCs retain transcription factor binding and chromatin accessibility independent of Brd4 function or expression...
April 16, 2018: Nature Cell Biology
https://www.readbyqxmd.com/read/29618782/etv2-tet1-tet2-complexes-induce-endothelial-cell-specific-robo4-expression-via-promoter-demethylation
#11
Toru Tanaka, Kohei Izawa, Yusuke Maniwa, Maki Okamura, Atsumasa Okada, Tomoko Yamaguchi, Keisuke Shirakura, Naoki Maekawa, Hayato Matsui, Kenji Ishimoto, Nobumasa Hino, Osamu Nakagawa, William C Aird, Hiroyuki Mizuguchi, Kenji Kawabata, Takefumi Doi, Yoshiaki Okada
Although transcription factors regulating endothelial cell (EC)-specific gene expression have been identified, it is not known how those factors induce EC-specificity. We previously reported that DNA hypomethylation of the proximal promoter elicits EC-specific expression of Roundabout4 (Robo4). However, the mechanisms establishing EC-specific hypomethylation of the Robo4 promoter remain unknown. In this study, we demonstrated that the hypermethylated Robo4 proximal promoter is demethylated as human iPS cells differentiate into endothelial cells...
April 4, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29617660/genomic-pathway-network-and-immunologic-features-distinguishing-squamous-carcinomas
#12
Joshua D Campbell, Christina Yau, Reanne Bowlby, Yuexin Liu, Kevin Brennan, Huihui Fan, Alison M Taylor, Chen Wang, Vonn Walter, Rehan Akbani, Lauren Averett Byers, Chad J Creighton, Cristian Coarfa, Juliann Shih, Andrew D Cherniack, Olivier Gevaert, Marcos Prunello, Hui Shen, Pavana Anur, Jianhong Chen, Hui Cheng, D Neil Hayes, Susan Bullman, Chandra Sekhar Pedamallu, Akinyemi I Ojesina, Sara Sadeghi, Karen L Mungall, A Gordon Robertson, Christopher Benz, Andre Schultz, Rupa S Kanchi, Carl M Gay, Apurva Hegde, Lixia Diao, Jing Wang, Wencai Ma, Pavel Sumazin, Hua-Sheng Chiu, Ting-Wen Chen, Preethi Gunaratne, Larry Donehower, Janet S Rader, Rosemary Zuna, Hikmat Al-Ahmadie, Alexander J Lazar, Elsa R Flores, Kenneth Y Tsai, Jane H Zhou, Anil K Rustgi, Esther Drill, Ronglei Shen, Christopher K Wong, Joshua M Stuart, Peter W Laird, Katherine A Hoadley, John N Weinstein, Myron Peto, Curtis R Pickering, Zhong Chen, Carter Van Waes
This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smoking and/or human papillomavirus (HPV). SCCs harbor 3q, 5p, and other recurrent chromosomal copy-number alterations (CNAs), DNA mutations, and/or aberrant methylation of genes and microRNAs, which are correlated with the expression of multi-gene programs linked to squamous cell stemness, epithelial-to-mesenchymal differentiation, growth, genomic integrity, oxidative damage, death, and inflammation...
April 3, 2018: Cell Reports
https://www.readbyqxmd.com/read/29582271/reduced-hydroxymethylation-characterizes-medulloblastoma-while-tet-and-idh-genes-are-differentially-expressed-within-molecular-subgroups
#13
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/29576538/a-critical-role-of-tet1-2-proteins-in-cell-cycle-progression-of-trophoblast-stem-cells
#14
Stephanie Chrysanthou, Claire E Senner, Laura Woods, Elena Fineberg, Hanneke Okkenhaug, Sarah Burge, Vicente Perez-Garcia, Myriam Hemberger
The ten-eleven translocation (TET) proteins are well known for their role in maintaining naive pluripotency of embryonic stem cells. Here, we demonstrate that, jointly, TET1 and TET2 also safeguard the self-renewal potential of trophoblast stem cells (TSCs) and have partially redundant roles in maintaining the epithelial integrity of TSCs. For the more abundantly expressed TET1, we show that this is achieved by binding to critical epithelial genes, notably E-cadherin, which becomes hyper-methylated and downregulated in the absence of TET1...
March 17, 2018: Stem Cell Reports
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
#15
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/29558748/ginsenoside-20-s-rg3-inhibits-the-warburg-effect-via-modulating-dnmt3a-mir-532-3p-hk2-pathway-in-ovarian-cancer-cells
#16
Yuanyuan Zhou, Xia Zheng, Jiaojiao Lu, Wei Chen, Xu Li, Le Zhao
BACKGROUND/AIMS: The Warburg effect is one of the main energy metabolism features supporting cancer cell growth. 20(S)-Rg3 exerts anti-tumor effect on ovarian cancer partly by inhibiting the Warburg effect. microRNAs are important regulators of the Warburg effect. However, the microRNA regulatory network mediating the anti-Warburg effect of 20(S)-Rg3 was largely unknown. METHODS: microRNA deep sequencing was performed to identify the 20(S)-Rg3-influenced microRNAs in SKOV3 ovarian cancer cells...
March 16, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29556496/tet-enzymes-variants-and-differential-effects-on-function
#17
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/29549908/ten-eleven-translocation-1-tet1-gene-is-a-potential-target-of-mir-21-5p-in-human-colorectal-cancer
#18
Ya-Wen Cheng, Chia-Jung Chou, Pei-Ming Yang
DNA 5-methylcytosine (5-mC) methylation, a key epigenetic mark, is critical for biological and pathological processes. Aberrant DNA methylation occurs in all tumor types and correlates with tumor suppressor gene silencing. DNA methylation is thought to be very stable, and active DNA demethylation remains a long-standing enigma. Recently, the ten-eleven translocation (TET) family of oxygenases are found to oxidize 5-mC to 5-hydroxymethylcytosine (5-hmC), which is prerequisite for active DNA demethylation. Both TET1 expression and global 5-hmC content are significantly reduced in colorectal cancer (CRC), the top leading cause of cancer-related death in the world...
March 2018: Surgical Oncology
https://www.readbyqxmd.com/read/29530881/imprinted-gene-dysregulation-in-a-tet1-null-mouse-model-is-stochastic-and-variable-in-the-germline-and-offspring
#19
Jennifer M SanMiguel, Lara K Abramowitz, Marisa S Bartolomei
Imprinted genes are expressed from one parental allele and regulated by differential DNA methylation at imprinting control regions (ICRs). ICRs are reprogrammed in the germline through erasure and re-establishment of DNA methylation. Although much is known about DNA methylation establishment, DNA demethylation is less well understood. Recently, the Ten-Eleven Translocation proteins (TET1-3) have been shown to initiate DNA demethylation, with Tet1 -/- mice exhibiting aberrant levels of imprinted gene expression and ICR methylation...
March 29, 2018: Development
https://www.readbyqxmd.com/read/29524149/editing-of-dna-methylation-using-dcas9-peptide-repeat-and-scfv-tet1-catalytic-domain-fusions
#20
Sumiyo Morita, Takuro Horii, Izuho Hatada
DNA methylation, one of the most studied epigenetic modifications, regulates many biological processes. Dysregulation of DNA methylation is implicated in the etiology of several diseases, such as cancer and imprinting diseases. Accordingly, technologies designed to manipulate DNA methylation at specific loci are very important, and many epigenome editing technologies have been developed, based on zinc finger proteins, TALEs, and CRISPR/dCas9 targeting. We describe a protocol to induce and assess DNA demethylation on a target gene...
2018: Methods in Molecular Biology
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