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Tet proteins

Bo Kong, Runbin Sun, Mingxing Huang, Monica D Chow, Xiao-Bo Zhong, Wen Xie, Yi-Horng Lee, Grace L Guo
The role of intestine-derived factors in promoting liver regeneration after partial hepatectomy (PHx) are not entirely known, but bile acids (BAs) and fibroblast growth factor 15 (Fgf15) that is highly expressed in the mouse ileum could promote hepatocyte proliferation. Fgf15 strongly suppresses the synthesis of BAs and emerging evidence indicates that Fgf15 is important for liver regeneration. The mechanisms by which Fgf15 promotes liver regeneration are unclear, but Fgf15 may do so indirectly by reducing BA levels and/or directly by promoting cell proliferation...
April 19, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
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
Ting Zhao, Jie Wu, Xiaohui Liu, Lei Zhang, Gang Chen, Haojie Lu
The histological typing of thymic epithelial tumours (TETs) still remains a challenge for surgical pathologists, especially when encountering borderline cases mainly focused on spindle cell types (including type A, atypical type A (aA), AB, and B3). A systematic proteomics analysis of TETs was performed using isobaric tags for relative and absolute quantification (iTRAQ) labeling coupled with two-dimensional liquid chromatography-tandem mass spectrometry (2D-LC-MS/MS). In total, 6479 and 6305 proteins were identified and quantified, respectively...
April 12, 2018: Analyst
Lv Xiong, Libo He, Lifei Luo, Yongming Li, Lanjie Liao, Rong Huang, Zuoyan Zhu, Yaping Wang
Grass carp reovirus (GCRV) causes huge economic loss to the grass carp cultivation industry but the mechanism remains largely unknown. In this study, we investigated the global and complement gene-specific DNA methylation in grass carp after GCRV infection aimed to uncover the mechanism underlying GCRV infection. The global DNA methylation level was increased after GCRV infection. Expression levels of enzymes involved in DNA methylation including DNA methyltransferase (DNMT), ten-eleven translocation proteins (TETs), and glycine N -methyltransferase (GNMT) were significantly altered after GCRV infection...
April 7, 2018: International Journal of Molecular Sciences
César García-Cruz, Candelaria Merino-Jiménez, Víctor Ceja, Jorge Aragón, Lourdes Siqueiros-Márquez, Juan Pablo Reyes-Grajeda, Cecilia Montañez
The Dp71 protein is the most abundant dystrophin in the central nervous system (CNS). Several dystrophin Dp71 isoforms have been described and are classified into three groups, each with a different C-terminal end. However, the functions of Dp71 isoforms remain unknown. In the present study, we analysed the effect of Dp71eΔ71 overexpression on neuronal differentiation of PC12 Tet-On cells. Overexpression of dystrophin Dp71eΔ71 stimulates neuronal differentiation, increasing the percentage of cells with neurites and neurite length...
April 3, 2018: Journal of Proteomics
Ashley Ramsawhook, Alexey Ruzov, Beth Coyle
The patterns of 5-methylcytosine (5mC) and its oxidized derivatives, 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine (5caC) are reportedly altered in a range of cancers. Likewise, Wilms' Tumor protein 1 (WT1), a transcription factor essential for urogenital, epicardium, and kidney development exhibits aberrant expression in multiple tumors. Interestingly, WT1 directly interacts with TET proteins that catalyze the enzymatic oxidation of 5mC and exhibits high affinity for 5caC-containing DNA substrates in vitro ...
2018: Frontiers in Cell and Developmental Biology
Peter Jessop, Alexey Ruzov, Martin Gering
5-methylcytosine (5mC) is the best understood DNA modification and is generally believed to be associated with repression of gene expression. Over the last decade, sequentially oxidized forms of 5mC (oxi-mCs) have been discovered within the genomes of vertebrates. Their discovery was accompanied by that of the ten-eleven translocation (TET) methylcytosine dioxygenases, the enzymes that catalyze the formation of the oxi-mCs. Although a number of studies performed on different vertebrate models and embryonic stem cells demonstrated that both TET enzymes and oxi-mCs are likely to be important for several developmental processes it is currently unclear whether their developmental roles are conserved among vertebrates...
2018: Frontiers in Cell and Developmental Biology
Karnika Singh, Qin Dong, Prakash S TimiriShanmugam, Sweaty Koul, Hari K Koul
Current therapies in Pancreatic Cancer (PaCa) are ineffective due to deregulated cell cycle driven by landscape mutations. In this study, we show for the first time that tetrandrine (TET) inhibits proliferation of the PaCa cells and inhibits PaCa tumor growth. TET inhibits cell cycle transition at G1/S boundary. TET increased levels of p21Cip1/Waf1 and p27Kip1 , had no effect on the levels of CDK4/6 proteins and decreased the levels of cyclin D1 and pRb proteins. TET resulted in changes in mRNA levels of cyclin D1 and p21Cip1/Waf1 but had no effect on the mRNA of p27Kip1 ...
March 29, 2018: Cancer Letters
Aylin Kanli, Murat Kasap, Kubra K Yoneten, Gurler Akpinar, Mehmet Dogan Gulkac
Tetracycline regulated protein expression in mammalian cells is a powerful tool to predict the physiological function, cellular localization, and stability of a protein. In addition, to predict metabolic networks affected by the expression of wild-type or mutant forms of proteins, researchers generally produce a single mammalian cell clone that can express the protein of interest under tetracycline control and study the changes occurring in overall proteome before and after expression of a protein of interest...
March 30, 2018: Journal of Cellular Biochemistry
Gaurav Raj Dwivedi, Anupam Maurya, Dharmendra Kumar Yadav, Vigyasa Singh, Feroz Khan, Mahendra Kumar Gupta, Mastan Singh, Mahendra P Darokar, Santosh Kumar Srivastava
The emergence of multidrug resistance (MDR) in Gram negative bacteria (GNB) and lack of novel classes of antibacterial agents have raised an immediate need to identify antibacterial agents, which can reverse the phenomenon of MDR. The purpose of present study was to evaluate synergy potential and understanding the drug resistance reversal mechanism of chanoclavine isolated from Ipomoea muricata against the multidrug resistant clinical isolate of Escherichia coli (MDREC). Although chanoclavine did not show antibacterial activity of its own, but in combination, it could reduce the minimum inhibitory concentration (MIC) of tetracycline (TET) up to 16 folds...
March 29, 2018: Journal of Biomolecular Structure & Dynamics
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
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
Gauri Shishodia, Sweaty Koul, Qin Dong, Hari K Koul
TNF-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis in cancer cells, but not in normal cells, as such is a promising therapeutic agent. However, therapeutic resistance limits its clinical use in many malignancies including prostate cancer (PCa). Strategies to sensitize cancer cells to TRAIL are urgently needed. We demonstrate here that small-molecule Tetrandrine (TET) potentially sensitizes previously resistant (LNCaP and C4-2B cells) and mildly sensitive (PC3 cells) PCa cells to TRAIL- induced apoptosis, and they do so by up-regulating mRNA expression and protein levels of death receptors Apo Trail R1 (DR4) and Apo Trail R2 (DR5)...
March 16, 2018: Molecular Cancer Therapeutics
Ruichuan Yin, Jiezhen Mo, Jiayin Dai, Hailin Wang
Nickel is found widely in the environment. It is an essential microelement but also toxic. However, nickel displays only weak genotoxicity and mutagenicity. Exploration of the epigenetic toxicity of nickel is extremely interesting. Iron(ii)- and 2-oxoglutarate-dependent Tet dioxygenases are a class of epigenetic enzymes that catalyze the oxidation of DNA 5-methylcytosine (5mC). Thus, they are critical for DNA demethylation and, importantly, are involved with nuclear reprogramming, embryonic development, and regulation of gene expression...
March 14, 2018: Metallomics: Integrated Biometal Science
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
Diego B Nobrega, Sohail Naushad, S Ali Naqvi, Larissa A Z Condas, Vineet Saini, John P Kastelic, Christopher Luby, Jeroen De Buck, Herman W Barkema
Emergence and spread of antimicrobial resistance is a major concern for the dairy industry worldwide. Objectives were to determine: (1) phenotypic and genotypic prevalence of drug-specific resistance for 25 species of non-aureus staphylococci, and (2) associations between presence of resistance determinants and antimicrobial resistance. Broth micro-dilution was used to determine resistance profiles for 1,702 isolates from 89 dairy herds. Additionally, 405 isolates were sequenced to screen for resistance determinants...
2018: Frontiers in Microbiology
Ailing Sui, Yisheng Zhong, Anna M Demetriades, Qing Lu, Yujuan Cai, Yushuo Gao, Yanji Zhu, Xi Shen, Bing Xie
PURPOSE: To assess the effect of inhibiting integrin α5β1 by ATN-161 on vascular endothelial growth factor (VEGF)-induced neovascularization (NV) and leakage causing retinal detachment in adult Tet/opsin/VEGF transgenic mice, and characterize the underlying mechanism of its function. METHOD: Retinas from adult Tet/opsin/VEGF transgenic mice and human retinal endothelial cells (HRECs) exposed to VEGF (treated with ATN-161 or PBS) were used to carry out immunofluorescence, RT-PCR and western blot to examine expression levels of integrin α5β1 and the NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome...
March 3, 2018: Graefe's Archive for Clinical and Experimental Ophthalmology
Yoshiyuki Seki
PR-domain containing protein 14 (PRDM14) is a site-specific DNA-binding protein and is required for establishment of pluripotency in embryonic stem cells (ESCs) and primordial germ cells (PGCs) in mice. DNA methylation status is regulated by the balance between de novo methylation and passive/active demethylation, and global DNA hypomethylation is closely associated with cellular pluripotency and totipotency. PRDM14 ensures hypomethylation in mouse ESCs and PGCs through two distinct layers, transcriptional repression of the DNA methyltransferases Dnmt3a/b/l and active demethylation by recruitment of TET proteins...
2018: Frontiers in Cell and Developmental Biology
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
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
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