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https://www.readbyqxmd.com/read/28074830/tet1-in-nucleus-accumbens-opposes-depression-and-anxiety-like-behaviors
#1
Jian Feng, Catherine J Pena, Immanuel Purushothaman, Olivia Engmann, Deena Walker, Amber N Brown, Orna Issler, Marie Doyle, Eileen Harrigan, Ezekiell Mouzon, Vincent Vialou, Li Shen, Meelad M Dawlaty, Rudolf Jaenisch, Eric J Nestler
Depression is a leading cause of disease burden, yet current therapies fully treat <50% of affected individuals. Increasing evidence implicates epigenetic mechanisms in depression and antidepressant action. Here, we examined a possible role for the DNA dioxygenase, ten eleven translocation protein 1 (TET1), in depression-related behavioral abnormalities. We applied chronic social defeat stress, an ethologically validated mouse model of depression-like behaviors, and examined Tet1 expression changes in nucleus accumbens (NAc), a key brain reward region...
January 11, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28043375/comparative-dynamics-of-5-methylcytosine-reprogramming-and-tet-family-expression-during-preimplantation-mammalian-development-in-mouse-and-sheep
#2
F Jafarpour, S M Hosseini, S Ostadhosseini, H Abbasi, A Dalman, M H Nasr-Esfahani
Despite previous assumption that paternal active DNA demethylation is an evolutionary conserved phenomenon in mammals, emerging studies in other species, particularly sheep, do not support this issue. Recently, ten eleven translocation (TET) enzymes have been suggested as intermediates in genome-wide DNA demethylation through the iterative conversion of five methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC)/5-formylcytosine/5-carboxylcytosine (5caC) derivatives. This study investigated whether TET enzymes and 5mC derivatives are also involved in dynamic reprogramming of early sheep embryos derived by fertilization...
February 2017: Theriogenology
https://www.readbyqxmd.com/read/28041878/epigenetic-modifiers-facilitate-induction-and-pluripotency-of-porcine-ipscs
#3
Jian Mao, Qian Zhang, Wei Deng, Hua Wang, Kai Liu, Haifeng Fu, Qiang Zhao, Xumin Wang, Lin Liu
Inadequate silencing of exogenous genes represents a major obstacle to complete epigenetic reprogramming of porcine-induced pluripotent stem cells (piPSCs) by conventional pluripotency transcription factors (OSKM). We tested the hypothesis that epigenetic modification by active DNA or histone demethylation or by inhibition of histone deacetylase would enhance reprogramming and exogenous gene silencing in piPSCs. piPSCs induced by OSKM in combination with epigenetic factors, specifically Ten-Eleven Translocation (Tet1 or Tet3) or lysine (K)-specific demethylase 3A (Kdm3a), expressed higher levels of Rex1 and other genes representing naive state and exhibited more open chromatin status, compared with those of OSKM controls...
January 10, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28038351/microrna-29-impairs-the-early-phase-of-reprogramming-process-by-targeting-active-dna-demethylation-enzymes-and-wnt-signaling
#4
Mariane Serra Fráguas, Reto Eggenschwiler, Jeannine Hoepfner, Josiane Lilian Dos Santos Schiavinato, Rodrigo Haddad, Lucila Habib Bourguignon Oliveira, Amélia Góes Araújo, Marco Antônio Zago, Rodrigo Alexandre Panepucci, Tobias Cantz
Somatic cell reprogramming by transcription factors and other modifiers such as microRNAs has opened broad avenues for the study of developmental processes, cell fate determination, and interplay of molecular mechanisms in signaling pathways. However, many of the mechanisms that drive nuclear reprogramming itself remain yet to be elucidated. Here, we analyzed the role of miR-29 during reprogramming in more detail. Therefore, we evaluated miR-29 expression during reprogramming of fibroblasts transduced with lentiviral OKS and OKSM vectors and we show that addition of c-MYC to the reprogramming factor cocktail decreases miR-29 expression levels...
December 19, 2016: Stem Cell Research
https://www.readbyqxmd.com/read/27981510/aberrant-cpg-methylation-mediates-abnormal-transcription-of-mao-a-induced-by-acute-and-chronic-l-3-4-dihydroxyphenylalanine-administration-in-sh-sy5y-neuronal-cells
#5
Zhaofei Yang, Xuan Wang, Jian Yang, Min Sun, Yong Wang, Xiaomin Wang
L-3,4-dihydroxyphenylalanine (L-dopa) remains the most effective drug for therapy of Parkinson's disease (PD); however, long-term use of it causes serious side effects. L-dopa-induced dyskinesia (LID) has consistently been related to L-dopa-derived excessive dopamine release, but the mechanisms have not been addressed very clear. Monoamine oxidase A (MAO-A) is one of the key enzymes in dopamine metabolism and therefore may be involved in L-dopa-induced side effects. And, epigenetic modification controls MAO-A gene transcription...
December 15, 2016: Neurotoxicity Research
https://www.readbyqxmd.com/read/27980707/a-fluorescence-polarization-biophysical-assay-for-the-naegleria-dna-hydroxylase-tet1
#6
Laura J Marholz, Wei Wang, Yu Zheng, Xiang Wang
The discovery of the 5-methylcytosine (5mC) oxidation by the ten-eleven translocation (Tet) protein family was an important advancement in our understanding of DNA-modified epigenetics. Potent inhibitors of these proteins are greatly desired for both the understanding of the functions of these enzymes and to serve as eventual therapeutic leads. So far, the discovery of such small molecules with high affinity has been quite limited. Original tools to screen for activity are greatly needed in order to accelerate this process...
February 11, 2016: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27975171/voluntary-physical-exercise-induces-expression-and-epigenetic-remodeling-of-vegfa-in-the-rat-hippocampus
#7
Christina A E Sølvsten, Frank de Paoli, Jane H Christensen, Anders L Nielsen
A healthy lifestyle, including regular physical exercise, is generally believed to improve cognitive function and enhance neurogenesis. Such physical exercise-induced effects are associated with increased brain expression of neurotrophic and growth factors. In the present study, we investigated Bdnf, Igf-1, Fgf-2, Egf, and VegfA messenger RNA (mRNA) expression levels in the male rat hippocampus and frontal cortex after 2 weeks of voluntary physical exercise. Whereas the expression of Fgf-2 was upregulated in the hippocampus and prefrontal cortex by physical exercise, the expression levels of Bdnf transcript 1, Bdnf transcript 4, Igf-1, and VegfA were upregulated only in the hippocampus...
December 14, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27930333/tet-proteins-influence-the-balance-between-neuroectodermal-and-mesodermal-fate-choice-by-inhibiting-wnt-signaling
#8
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 20, 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
#9
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
#10
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...
December 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
#11
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
#12
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...
January 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27863519/tet-dependent-regulation-of-retrotransposable-elements-in-mouse-embryonic-stem-cells
#13
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
#14
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
#15
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
#16
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 1, 2016: Genes & Development
https://www.readbyqxmd.com/read/27848971/epigenetic-and-genetic-components-of-height-regulation
#17
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
#18
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
#19
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...
March 2017: 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
#20
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
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