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https://www.readbyqxmd.com/read/27930333/tet-proteins-influence-the-balance-between-neuroectodermal-and-mesodermal-fate-choice-by-inhibiting-wnt-signaling
#1
Xiang Li, Xiaojing Yue, William A Pastor, Lizhu Lin, Romain Georges, Lukas Chavez, Sylvia M Evans, Anjana Rao
TET-family dioxygenases catalyze conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) and oxidized methylcytosines in DNA. Here, we show that mouse embryonic stem cells (mESCs), either lacking Tet3 alone or with triple deficiency of Tet1/2/3, displayed impaired adoption of neural cell fate and concomitantly skewed toward cardiac mesodermal fate. Conversely, ectopic expression of Tet3 enhanced neural differentiation and limited cardiac mesoderm specification. Genome-wide analyses showed that Tet3 mediates cell-fate decisions by inhibiting Wnt signaling, partly through promoter demethylation and transcriptional activation of the Wnt inhibitor secreted frizzled-related protein 4 (Sfrp4)...
December 5, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27923996/binding-of-mbd-proteins-to-dna-blocks-tet1-function-thereby-modulating-transcriptional-noise
#2
Anne K Ludwig, Peng Zhang, Florian D Hastert, Stephanie Meyer, Cathia Rausch, Henry D Herce, Udo Müller, Anne Lehmkuhl, Ines Hellmann, Carina Trummer, Christian Storm, Heinrich Leonhardt, M Cristina Cardoso
Aberrant DNA methylation is a hallmark of various human disorders, indicating that the spatial and temporal regulation of methylation readers and modifiers is imperative for development and differentiation. In particular, the cross-regulation between 5-methylcytosine binders (MBD) and modifiers (Tet) has not been investigated. Here, we show that binding of Mecp2 and Mbd2 to DNA protects 5-methylcytosine from Tet1-mediated oxidation. The mechanism is not based on competition for 5-methylcytosine binding but on Mecp2 and Mbd2 directly restricting Tet1 access to DNA...
December 6, 2016: Nucleic Acids Research
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/27900099/effect-of-cytostatic-proline-rich-polypeptide-1-on-tumor-suppressors-of-inflammation-pathway-signaling-in-chondrosarcoma
#4
Karina Galoian, Shihua Luo, Amir Qureshi, Parthik Patel, Rachel Price, Ashlyn S Morse, Gor Chailyan, Silva Abrahamyan, H T Temple
Cytokines produced in the tumour microenvironment exert an important role in cancer pathogenesis and in the inhibition of disease progression. Cancer of the cartilage is termed metastatic chondrosarcoma; however, the signaling events resulting in mesenchymal cell transformation to sarcoma have yet to be fully elucidated. The present study aimed to characterize the cytokine expression profile in the human JJ012 chondrosarcoma cell line, as well as the effect of cytostatic proline-rich polypeptide-1 (PRP-1). Western blot experiments demonstrated that the levels of suppressor of cytokine signaling 3 (SOCS3) were upregulated in chondrocytes compared with chondrosarcoma cells...
November 2016: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/27889612/tet1-gper-pi3k-akt-pathway-is-involved-in-insulin-driven-endometrial-cancer-cell-proliferation
#5
Bing-Ying Xie, Qiao-Ying Lv, Cheng-Cheng Ning, Bing-Yi Yang, Wei-Wei Shan, Ya-Li Cheng, Chao Gu, Xue-Zhen Luo, Zhen-Bo Zhang, Xiao-Jun Chen, Xiao-Wei Xi, You-Ji Feng
Large amount of clinical evidence has demonstrated that insulin resistance is closely related to oncogenesis of endometrial cancer (EC). Despite recent studies showed the up-regulatory role of insulin in G protein-coupled estrogen receptor (GPER/GPR30) expression, GPER expression was not decreased compared to control when insulin receptor was blocked even in insulin treatment. The purpose of this study was to explore the possible mechanism by which insulin up-regulates GPER that drives EC cell proliferation...
November 23, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27863519/tet-dependent-regulation-of-retrotransposable-elements-in-mouse-embryonic-stem-cells
#6
Lorenzo de la Rica, Özgen Deniz, Kevin C L Cheng, Christopher D Todd, Cristina Cruz, Jonathan Houseley, Miguel R Branco
BACKGROUND: Ten-eleven translocation (TET) enzymes oxidise DNA methylation as part of an active demethylation pathway. Despite extensive research into the role of TETs in genome regulation, little is known about their effect on transposable elements (TEs), which make up nearly half of the mouse and human genomes. Epigenetic mechanisms controlling TEs have the potential to affect their mobility and to drive the co-adoption of TEs for the benefit of the host. RESULTS: We performed a detailed investigation of the role of TET enzymes in the regulation of TEs in mouse embryonic stem cells (ESCs)...
November 18, 2016: Genome Biology
https://www.readbyqxmd.com/read/27857218/tet1-dependent-epigenetic-modification-of-bdnf-expression-in-dorsal-horn-neurons-mediates-neuropathic-pain-in-rats
#7
Ming-Chun Hsieh, Cheng-Yuan Lai, Yu-Cheng Ho, Hsueh-Hsiao Wang, Jen-Kun Cheng, Yat-Pang Chau, Hsien-Yu Peng
Ten-eleven translocation methylcytosine dioxygenase 1 (Tet1) mediates the conversion of 5-methylcytosine (5 mC) to 5-hydroxymethylcytosine (5 hmC), hence promoting DNA demethylation. Although recent studies have linked the DNA demethylation of specific genes to pain hypersensitivity, the role of spinal Tet1-dependent DNA demethylation in nociception hypersensitivity development remains elusive. Here, we report correlated with behavioral allodynia, spinal nerve ligation (SNL) upregulated Tet1 expression in dorsal horn neurons that hydroxylate 5 mC to 5 hmC at CpG dinucleotides in the bdnf promoter to promote spinal BDNF expression at day 7 after operation...
November 18, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27857213/the-modification-of-tet1-in-male-germline-stem-cells-and-interact-with-pcna-hdac1-to-promote-their-self-renewal-and-proliferation
#8
Liming Zheng, Yuanxin Zhai, Na Li, Fanglin Ma, Haijing Zhu, Xiaomin Du, Guangpeng Li, Jinlian Hua
Epigenetic modification plays key roles in spermatogenesis, especially DNA methylation dynamic is important in sustaining normal spermatogenesis. Ten-eleven translocation 1 (Tet1) is not only a key demethylase, which works in specific gene regions, but also crosstalks with partners to regulate epigenetic progress as protein complexes. Dairy goat is an important livestock in China, while the unstable culture system in vitro inhibits optimization of new dairy goat species. The study of epigenetic modification in male germline stem cells (mGSCs) is beneficial to the optimization of adult stem cell culture system in vitro, and the improvement of sperm quality and breeding of selected livestock...
November 18, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27856615/epigenetic-regulation-of-intestinal-stem-cells-by-tet1-mediated-dna-hydroxymethylation
#9
Rinho Kim, Karyn L Sheaffer, Inchan Choi, Kyoung-Jae Won, Klaus H Kaestner
Methylated cytosines are associated with gene silencing. The ten-eleven translocation (TET) hydroxylases, which oxidize methylated cytosines to 5-hydroxymethylcytosine (5hmC), are essential for cytosine demethylation. Gene silencing and activation are critical for intestinal stem cell (ISC) maintenance and differentiation, but the potential role of TET hydroxylases in these processes has not yet been examined. Here, we generated genome-wide maps of the 5hmC mark in ISCs and their differentiated progeny. Genes with high levels of hydroxymethylation in ISCs are strongly associated with Wnt signaling and developmental processes...
November 17, 2016: Genes & Development
https://www.readbyqxmd.com/read/27848971/epigenetic-and-genetic-components-of-height-regulation
#10
Stefania Benonisdottir, Asmundur Oddsson, Agnar Helgason, Ragnar P Kristjansson, Gardar Sveinbjornsson, Arna Oskarsdottir, Gudmar Thorleifsson, Olafur B Davidsson, Gudny A Arnadottir, Gerald Sulem, Brynjar O Jensson, Hilma Holm, Kristjan F Alexandersson, Laufey Tryggvadottir, G Bragi Walters, Sigurjon A Gudjonsson, Lucas D Ward, Jon K Sigurdsson, Paul D Iordache, Michael L Frigge, Thorunn Rafnar, Augustine Kong, Gisli Masson, Hannes Helgason, Unnur Thorsteinsdottir, Daniel F Gudbjartsson, Patrick Sulem, Kari Stefansson
Adult height is a highly heritable trait. Here we identified 31.6 million sequence variants by whole-genome sequencing of 8,453 Icelanders and tested them for association with adult height by imputing them into 88,835 Icelanders. Here we discovered 13 novel height associations by testing four different models including parent-of-origin (|β|=0.4-10.6 cm). The minor alleles of three parent-of-origin signals associate with less height only when inherited from the father and are located within imprinted regions (IGF2-H19 and DLK1-MEG3)...
November 16, 2016: Nature Communications
https://www.readbyqxmd.com/read/27848178/dysregulation-of-tet2-in-hematologic-malignancies
#11
REVIEW
Shigeru Chiba
The TET dioxygenases, TET1, TET2, and TET3, catalyze transfer of an oxygen atom to the methyl group of 5-methylcytocine (5-mC), converting it to 5-hydroxymethylcytocine (5-hmC). Among the genes encoding these enzymes, ten-eleven translocation 2 (TET2) is frequently mutated somatically in both myeloid and lymphoid malignancies. Because these TET2 mutations result in the impairment of the dioxygenase activity of TET2, it is thought that these mutations interfere with 5-mC to 5-hmC conversion. There is ample evidence indicating that TET2 mutations are a driver of tumorigenesis in blood cells and that TET2 mutations are often acquired at the hematopoietic stem/early progenitor cell stage...
November 15, 2016: International Journal of Hematology
https://www.readbyqxmd.com/read/27846738/association-of-tet1-expression-with-colorectal-cancer-progression
#12
Yiping Tian, Feixia Pan, Xiaohui Sun, Meifu Gan, Aifen Lin, Dandan Zhang, Yimin Zhu, Maode Lai
OBJECTIVE: The ten-eleven translocation (TET) proteins, as methylcytosine dioxygenases, catalyze 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC). The altered expression of TET1 disrupts the balance between DNA methylation and demethylation. This alteration has been reported to be associated with carcinogenesis in various malignancies. The aim of the present study was to investigate changes in expression and the role of TET1 in colorectal cancer (CRC). MATERIAL AND METHODS: A total of 109 CRC patients who underwent radical surgical colon resection were enrolled...
November 16, 2016: Scandinavian Journal of Gastroenterology
https://www.readbyqxmd.com/read/27835592/epigenetic-upregulation-of-arl4c-due-to-dna-hypomethylation-in-the-3-untranslated-region-promotes-tumorigenesis-of-lung-squamous-cell-carcinoma
#13
Shinsuke Fujii, Keiko Shinjo, Shinji Matsumoto, Takeshi Harada, Satoshi Nojima, Sunao Sato, Yu Usami, Satoru Toyosawa, Eiichi Morii, Yutaka Kondo, Akira Kikuchi
ADP-ribosylation factor (ARF)-like 4c (ARL4C) expression, induced by a combination of Wnt/β-catenin and EGF/Ras signaling, has been demonstrated to form epithelial morphogenesis. ARL4C overexpression, due to Wnt/β-catenin and EGF/Ras signaling alterations, was involved in tumorigenesis. It was also reported that ARL4C expression correlates with DNA hypomethylation in the 3'-untranslated region (UTR) of ARL4C gene during lymphogenesis. The current study was conducted to investigate the expression and functions of ARL4C due to DNA hypomethylation in lung and tongue cancers...
November 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27805801/tet1-mediated-oxidation-of-5-formylcytosine-5fc-to-5-carboxycytosine-5cac-in-rna
#14
Maria Basanta-Sanchez, Rui Wang, Zhenzhen Liu, Xiaohan Ye, Minyong Li, Xiaodong Shi, Paul Agris, Yubin Zhou, Yun Huang, Jia Sheng
It has been revealed recently that 5-methylcytosine (5mC) in mRNA, similar as in DNA, can also be oxidized to produce 5-hydroxymethylcytosine (5hmC) and 5-formylcytosine (5fC), implying the potential regulatory roles of this post-transcriptional RNA modification. In this study, we demonstrate the in vitro oxidation of 5fC to 5-carboxycytidine (5caC) by the catalytic domain of mammalian ten-eleven translocation enzyme (TET1) in different RNA contexts. We observed that this oxidation process has very low sequence dependence and can take place in single stranded, double stranded or hairpin forms of RNA sequences, although the overall conversion yields are low...
November 2, 2016: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/27778125/ten-eleven-translocation-1-and-2-confer-overlapping-transcriptional-programs-for-the-proliferation-of-cultured-adult-neural-stem-cells
#15
Koji Shimozaki
Adult neurogenesis originates from neural stem cells (NSCs) in specific regions of the adult brain. The molecular mechanisms that control the self-renewal and multipotency of NSCs have not been fully elucidated. In recent years, emerging evidence has revealed that ten-eleven translocation (TET) family DNA dioxygenases TET1 and TET2 play important roles in the central nervous system. Here, I present evidence that Tet1 and Tet2 are expressed in cultured NSCs derived from adult mouse brain and play an important role in the proliferative self-renewal of NSCs in an undifferentiated state...
October 24, 2016: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/27746118/molecular-features-of-doxorubicin-resistance-development-in-colorectal-cancer-cx-1-cell-line
#16
Raimonda Kubiliūtė, Indrė Šulskytė, Kristina Daniūnaitė, Rimantas Daugelavičius, Sonata Jarmalaitė
BACKGROUND AND AIM: Resistance to chemotherapy is the key obstacle to the effective treatment of various cancers. Accumulating evidence suggests significant involvement of the epithelial-to-mesenchymal transition (EMT) in the chemoresistance of most cancer types. This study aimed at analyzing the gene expression profile of doxorubicin (DOX)-resistant colorectal cancer cells CX-1. MATERIALS AND METHODS: DOX-resistant CX-1 cell sublines were acquired by stepwise increment of DOX concentrations in cell growth media...
2016: Medicina
https://www.readbyqxmd.com/read/27739137/zeb2-regulates-cell-fate-at-the-exit-from-epiblast-state-in-mouse-embryonic-stem-cells
#17
Agata Stryjewska, Ruben Dries, Tim Pieters, Griet Verstappen, Andrea Conidi, Kathleen Coddens, Annick Francis, Lieve Umans, Wilfred F J Van IJcken, Geert Berx, Leo A van Grunsven, Frank G Grosveld, Steven Goossens, Jody J Haigh, Danny Huylebroeck
In human embryonic stem cells (ESCs) the transcription factor Zeb2 regulates neuroectoderm versus mesendoderm formation, but it is unclear how Zeb2 affects the global transcriptional regulatory network in these cell-fate decisions. We generated Zeb2 knockout (KO) mouse ESCs, subjected them as embryoid bodies (EBs) to neural and general differentiation and carried out temporal RNA-sequencing (RNA-seq) and reduced representation bisulfite sequencing (RRBS) analysis in neural differentiation. This shows that Zeb2 acts preferentially as a transcriptional repressor associated with developmental progression and that Zeb2 KO ESCs can exit from their naïve state...
October 14, 2016: Stem Cells
https://www.readbyqxmd.com/read/27733505/tet1-modulates-h4k16-acetylation-by-controlling-auto-acetylation-of-hmof-to-affect-gene-regulation-and-dna-repair-function
#18
Jianing Zhong, Xianfeng Li, Wanshi Cai, Yan Wang, Shanshan Dong, Jie Yang, Jian'an Zhang, Nana Wu, Yuanyuan Li, Fengbiao Mao, Cheng Zeng, Jinyu Wu, Xingzhi Xu, Zhong Sheng Sun
The Ten Eleven Translocation 1 (TET1) protein is a DNA demethylase that regulates gene expression through altering statue of DNA methylation. However, recent studies have demonstrated that TET1 could modulate transcriptional expression independent of its DNA demethylation activity; yet, the detailed mechanisms underlying TET1's role in such transcriptional regulation remain not well understood. Here, we uncovered that Tet1 formed a chromatin complex with histone acetyltransferase Mof and scaffold protein Sin3a in mouse embryonic stem cells by integrative genomic analysis using publicly available ChIP-seq data sets and a series of in vitro biochemical studies in human cell lines...
October 12, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27708396/erk-c-jun-recruits-tet1-to-induce-zta-expression-and-epstein-barr-virus-reactivation-through-dna-demethylation
#19
Wei Zhang, Dongjie Han, Pin Wan, Pan Pan, Yanhua Cao, Yingle Liu, Kailang Wu, Jianguo Wu
DNA demethylation plays an essential role in the reactivation of Epstein-Barr virus (EBV) from latency infection. However, it is unclear how epigenetic modification is initiated in responding to stimuli. Here, we demonstrate that ERK/c-Jun signaling is involved in DNA demethylation of EBV immediate early (IE) gene Zta in response to 12-O-Tetradecanoylphorbol-13-acetate (TPA) stimulation. Remarkably, Ser73 phosphorylation of c-Jun facilitates Zta promoter demethylation and EBV reactivation, whereas knockdown of c-Jun attenuates Zta demethylation and viral reactivation...
October 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27708339/corrigendum-epigenetic-inactivation-of-the-cpg-demethylase-tet1-as-a-dna-methylation-feedback-loop-in-human-cancers
#20
Lili Li, Chen Li, Haitao Mao, Zhenfang Du, Wai Yee Chan, Paul Murray, Bing Luo, Anthony Tc Chan, Tony Sk Mok, Francis Kl Chan, Richard F Ambinder, Qian Tao
No abstract text is available yet for this article.
October 6, 2016: Scientific Reports
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