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https://www.readbyqxmd.com/read/27899822/mir-150-exerts-antileukemia-activity-in-vitro-and-in-vivo-through-regulating-genes-in-multiple-pathways
#1
Zhi Hong Fang, Si Li Wang, Jin Tao Zhao, Zhi Juan Lin, Lin Yan Chen, Rui Su, Si Ting Xie, Bing Z Carter, Bing Xu
MicroRNAs, a class of small noncoding RNAs, have been implicated to regulate gene expression in virtually all important biological processes. Although accumulating evidence demonstrates that miR-150, an important regulator in hematopoiesis, is deregulated in various types of hematopoietic malignancies, the precise mechanisms of miR-150 action are largely unknown. In this study, we found that miR-150 is downregulated in samples from patients with acute lymphoblastic leukemia, acute myeloid leukemia, and chronic myeloid leukemia, and normalized after patients achieved complete remission...
September 22, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27880907/tet3-mediated-dna-demethylation-contributes-to-the-direct-conversion-of-fibroblast-to-functional-neuron
#2
Juan Zhang, Shuangquan Chen, Dongming Zhang, Zixiao Shi, Hong Li, Tongbiao Zhao, Baoyang Hu, Qi Zhou, Jianwei Jiao
The direct conversion of somatic cells to neurons by bypassing the multipotent cell state may be a powerful approach for personalized medicine. In addition to neuronal transcription factors and multiple small molecules, we find that epigenetic modification also contributes to the direct conversion of fibroblasts to neurons. Here, we show that Tet3, a DNA dioxygenase, can rapidly and efficiently convert fibroblasts directly into functional neurons. The induced neurons (iNs) express pan and mature neuronal markers such as Tuj1, Synapsin, and neuronal nuclei (NeuN)...
November 22, 2016: Cell Reports
https://www.readbyqxmd.com/read/27869820/tet-proteins-regulate-the-lineage-specification-and-tcr-mediated-expansion-of-inkt-cells
#3
Ageliki Tsagaratou, Edahí González-Avalos, Sini Rautio, James P Scott-Browne, Susan Togher, William A Pastor, Ellen V Rothenberg, Lukas Chavez, Harri Lähdesmäki, Anjana Rao
TET proteins oxidize 5-methylcytosine in DNA to 5-hydroxymethylcytosine and other oxidation products. We found that simultaneous deletion of Tet2 and Tet3 in mouse CD4(+)CD8(+) double-positive thymocytes resulted in dysregulated development and proliferation of invariant natural killer T cells (iNKT cells). Tet2-Tet3 double-knockout (DKO) iNKT cells displayed pronounced skewing toward the NKT17 lineage, with increased DNA methylation and impaired expression of genes encoding the key lineage-specifying factors T-bet and ThPOK...
November 21, 2016: Nature Immunology
https://www.readbyqxmd.com/read/27869616/tet2-and-tet3-cooperate-with-b-lineage-transcription-factors-to-regulate-dna-modification-and-chromatin-accessibility
#4
Chan-Wang Jerry Lio, Jiayuan Zhang, Edahí González-Avalos, Patrick G Hogan, Xing Chang, Anjana Rao
Ten-eleven translocation (TET) enzymes oxidize 5-methylcytosine, facilitating DNA demethylation and generating new epigenetic marks. Here we show that concomitant loss of Tet2 and Tet3 in mice at early B cell stage blocked the pro- to pre-B cell transition in the bone marrow, decreased Irf4 expression and impaired the germline transcription and rearrangement of the Igκ locus. Tet2/3-deficient pro-B cells showed increased CpG methylation at the Igκ 3' and distal enhancers that was mimicked by depletion of E2A or PU...
November 21, 2016: ELife
https://www.readbyqxmd.com/read/27852070/epigenetic-silencing-of-tet2-and-tet3-induces-an-emt-like-process-in-melanoma
#5
Fuxing Gong, Yu Guo, Yiqian Niu, Jiawei Jin, Xiaojuan Zhang, Xiaoqian Shi, Limeng Zhang, Runting Li, Longxin Chen, Runlin Z Ma
Epithelial-Mesenchymal Transition (EMT) is a critical step in the progression of cancer. Malignant melanoma, a cancer developed from pigmented melanocytes, metastasizes through an EMT-like process. Ten-eleven translocation (TET) enzymes, catalyzing the conversion of 5-methylcytosine (5mC) to 5-hydroxylmethylcytosine (5-hmC), are down regulated in melanoma. However, their roles in the progression and the EMT-like process of melanoma are not fully understood. Here we report that DNA methylation induced silencing of TET2 and TET3 are responsible for the EMT-like process and the metastasis of melanoma...
November 12, 2016: Oncotarget
https://www.readbyqxmd.com/read/27848178/dysregulation-of-tet2-in-hematologic-malignancies
#6
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/27729528/retinol-and-ascorbate-drive-erasure-of-epigenetic-memory-and-enhance-reprogramming-to-na%C3%A3-ve-pluripotency-by-complementary-mechanisms
#7
Timothy Alexander Hore, Ferdinand von Meyenn, Mirunalini Ravichandran, Martin Bachman, Gabriella Ficz, David Oxley, Fátima Santos, Shankar Balasubramanian, Tomasz P Jurkowski, Wolf Reik
Epigenetic memory, in particular DNA methylation, is established during development in differentiating cells and must be erased to create naïve (induced) pluripotent stem cells. The ten-eleven translocation (TET) enzymes can catalyze the oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) and further oxidized derivatives, thereby actively removing this memory. Nevertheless, the mechanism by which the TET enzymes are regulated, and the extent to which they can be manipulated, are poorly understood...
October 11, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27713569/dioxin-induces-ahr-dependent-robust-dna-demethylation-of-the-cyp1a1-promoter-via-tdg-in-the-mouse-liver
#8
Hesbon Z Amenya, Chiharu Tohyama, Seiichiroh Ohsako
The aryl hydrocarbon receptor (Ahr) is a highly conserved nuclear receptor that plays an important role in the manifestation of toxicity induced by polycyclic aromatic hydrocarbons. As a xenobiotic sensor, Ahr is involved in chemical biotransformation through activation of drug metabolizing enzymes. The activated Ahr cooperates with coactivator complexes to induce epigenetic modifications at target genes. Thus, it is conceivable that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a potent Ahr ligand, may elicit robust epigenetic changes in vivo at the Ahr target gene cytochrome P450 1a1 (Cyp1a1)...
October 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27692563/low-dose-hydralazine-prevents-fibrosis-in-a-murine-model-of-acute-kidney-injury-to-chronic-kidney-disease-progression
#9
Björn Tampe, Ulrike Steinle, Désirée Tampe, Julienne L Carstens, Peter Korsten, Elisabeth M Zeisberg, Gerhard A Müller, Raghu Kalluri, Michael Zeisberg
Acute kidney injury (AKI) and progressive chronic kidney disease (CKD) are intrinsically tied syndromes. In this regard, the acutely injured kidney often does not achieve its full regenerative capacity and AKI directly transitions into progressive CKD associated with tubulointerstitial fibrosis. Underlying mechanisms of such AKI-to-CKD progression are still incompletely understood and specific therapeutic interventions are still elusive. Because epigenetic modifications play a role in maintaining tissue fibrosis, we used a murine model of ischemia-reperfusion injury to determine whether aberrant promoter methylation of RASAL1 contributes causally to the switch between physiological regeneration and tubulointerstitial fibrogenesis, a hallmark of AKI-to-CKD progression...
September 27, 2016: Kidney International
https://www.readbyqxmd.com/read/27627619/tet3-mediates-alterations-in-the-epigenetic-marker-5hmc-and-akt-pathway-in-steroid-associated-osteonecrosis
#10
Jie Zhao, Xin-Long Ma, Jian-Xiong Ma, Lei Sun, Bin Lu, Ying Wang, Guo-Sheng Xing, Yan Wang, Ben-Chao Dong, Li-Yan Xu, Ming-Jie Kuang, Lin Fu, Hao-Hao Bai, Yue Ma, Wei-Lin Jin
Steroid-associated osteonecrosis (SAON) is one of the common complications of clinical glucocorticoid (GC) administration, with osteocyte apoptosis appearing as the primary histopathological lesion. However, the precise mechanism underlying SAON remains unknown. Epigenetic modification may be a major cause of SAON. Recently, cumulative research revealed that Ten-Eleven Translocation (TET) proteins can catalyze the conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) and then alter the epigenetic state of DNA...
September 13, 2016: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/27587280/analysis-of-the-machinery-and-intermediates-of-the-5hmc-mediated-dna-demethylation-pathway-in-aging-on-samples-from-the-mark-age-study
#11
Elisabetta Valentini, Michele Zampieri, Marco Malavolta, Maria Giulia Bacalini, Roberta Calabrese, Tiziana Guastafierro, Anna Reale, Claudio Franceschi, Antti Hervonen, Bernhard Koller, Jürgen Bernhardt, P Eline Slagboom, Olivier Toussaint, Ewa Sikora, Efstathios S Gonos, Nicolle Breusing, Tilman Grune, Eugène Jansen, Martijn E T Dollé, María Moreno-Villanueva, Thilo Sindlinger, Alexander Bürkle, Fabio Ciccarone, Paola Caiafa
Gradual changes in the DNA methylation landscape occur throughout aging virtually in all human tissues. A widespread reduction of 5-methylcytosine (5mC), associated with highly reproducible site-specific hypermethylation, characterizes the genome in aging. Therefore, an equilibrium seems to exist between general and directional deregulating events concerning DNA methylation controllers, which may underpin the age-related epigenetic changes. In this context, 5mC-hydroxylases (TET enzymes) are new potential players...
August 29, 2016: Aging
https://www.readbyqxmd.com/read/27523618/immune-regulator-mcpip1-modulates-tet-expression-during-early-neocortical-development
#12
Huihui Jiang, Xiaohui Lv, Xuepei Lei, Ying Yang, Xin Yang, Jianwei Jiao
MCPIP1 is a recently identified immune regulator that plays critical roles in preventing immune disorders, and is also present in the brain. Currently an unresolved question remains as to how MCPIP1 performs its non-immune functions in normal brain development. Here, we report that MCPIP1 is abundant in neural progenitor cells (NPCs) and newborn neurons during the early stages of neurogenesis. The suppression of MCPIP1 expression impairs normal neuronal differentiation, cell-cycle exit, and concomitant NPC proliferation...
September 13, 2016: Stem Cell Reports
https://www.readbyqxmd.com/read/27425624/tet3-inhibits-type-i-ifn-production-independent-of-dna-demethylation
#13
Shengjie Xue, Chang Liu, Xiujie Sun, Weiyun Li, Chi Zhang, Xin Zhou, Yao Lu, Jun Xiao, Chunyang Li, Xiaoyan Xu, Bing Sun, Guoliang Xu, Hongyan Wang
Type I interferons (IFNs) play both beneficial and harmful roles in antiviral responses. Precise regulation of host type I IFNs is thus needed to prevent immune dysregulation. Here, we find that the DNA demethylase TET3 is a negative regulator of IFN-β in response to poly(I:C) stimulation or viral infection. Deletion of TET3 enhances antiviral responses, with elevated expression of IFN-β and IFN-stimulated genes. The catalytic domain of TET3 was critical for the suppression of IFN-β production, but TET3 enzymatic activity was dispensable...
July 26, 2016: Cell Reports
https://www.readbyqxmd.com/read/27418527/tet1-and-tet3-are-essential-in-induction-of-th2-type-immunity-partly-through-regulation-of-il-4-13a-expression-in-zebrafish-model
#14
Chao Yang, Zhuo Li, Wei Kang, Yu Tian, Yuzhu Yan, Wei Chen
It has been considered that epigenetic modulation can affect a diverse array of cellular activities, in which ten eleven translocation (TET) methylcytosine dioxygenase family members refer to a group of fundamental components involved in catalyzation of 5-hydroxymethylcytosine and modification of gene expression. Even though the function of TET proteins has been gradually revealed, their roles in immune regulation are still largely unknown. Recent studies provided clues that TET2 could regulate several innate immune-related inflammatory mediators in mammals...
October 10, 2016: Gene
https://www.readbyqxmd.com/read/27353491/differential-gene-expression-in-mouse-spermatogonial-stem-cells-and-embryonic-stem-cells
#15
Yinshan Bai, Meiying Feng, Shanshan Liu, Hengxi Wei, Li Li, Xianwei Zhang, Chao Shen, Shouquan Zhang, Ningfang Ma
Mouse spermatogonial stem cells (mSSCs) may be reprogrammed to become pluripotent stem cells under in vitro culture conditions, due to epigenetic modifications, which are closely associated with the expression of transcription factors and epigenetic factors. Thus, this study was conducted to compare the gene expression of transcription factors and epigenetic factors in mSSCs and mouse embryonic stem cells (mESCs). Firstly, the freshly isolated mSSCs [mSSCs (f)] were enriched by magnetic-activated cell sorting with Thy1...
August 2016: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/27207907/acute-and-chronic-electroconvulsive-seizures-ecs-differentially-regulate-the-expression-of-epigenetic-machinery-in-the-adult-rat-hippocampus
#16
Madhavi Pusalkar, Shreya Ghosh, Minal Jaggar, Basma Fatima Anwar Husain, Sanjeev Galande, Vidita A Vaidya
BACKGROUND: Electroconvulsive seizure treatment is a fast-acting antidepressant therapy that evokes rapid transcriptional, neurogenic, and behavioral changes. Epigenetic mechanisms contribute to altered gene regulation, which underlies the neurogenic and behavioral effects of electroconvulsive seizure. We hypothesized that electroconvulsive seizure may modulate the expression of epigenetic machinery, thus establishing potential alterations in the epigenetic landscape. METHODS: We examined the influence of acute and chronic electroconvulsive seizure on the gene expression of histone modifiers, namely histone acetyltransferases, histone deacetylases, histone methyltransferases, and histone (lysine) demethylases as well as DNA modifying enzymes, including DNA methyltransferases, DNA demethylases, and methyl-CpG-binding proteins in the hippocampi of adult male Wistar rats using quantitative real time-PCR analysis...
May 17, 2016: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27198154/regulation-of-mir-200c-and-mir-141-by-methylation-in-prostate-cancer
#17
Seodhna M Lynch, Karla M O'Neill, Michael M McKenna, Colum P Walsh, Declan J McKenna
BACKGROUND: In prostate cancer (PCa), abnormal expression of several microRNAs (miRNAs) has been previously reported. Increasing evidence shows that aberrant epigenetic regulation of miRNAs is a contributing factor to their altered expression in cancer. In this study, we investigate whether expression of miR-200c and miR-141 in PCa is related to the DNA methylation status of their promoter. METHODS: PCR analysis of miR-200c and miR-141, and CpG methylation analysis of their common promoter, was performed in PCa cell-lines and in archived prostate biopsy specimens...
September 2016: Prostate
https://www.readbyqxmd.com/read/27141829/tet3-inhibits-tgf-%C3%AE-1-induced-epithelial-mesenchymal-transition-by-demethylating-mir-30d-precursor-gene-in-ovarian-cancer-cells
#18
Zhongxue Ye, Jie Li, Xi Han, Huilian Hou, He Chen, Xia Zheng, Jiaojiao Lu, Lijie Wang, Wei Chen, Xu Li, Le Zhao
BACKGROUND: Abnormal DNA methylation/demethylation is recognized as a hallmark of cancer. TET (ten-eleven translocation) family members are novel DNA demethylation related proteins that dysregulate in multiple malignances. However, their effects on ovarian cancer remain to be elucidated. METHODS: The changes of TET family members during TGF-β1-induced epithelial-mesenchymal transition (EMT) in SKOV3 and 3AO ovarian cancer cells were detected. TET3 was ectopically expressed in TGF-β1-treated ovarian cancer cells to examine its effect on TGF-β1-induced EMT phenotype...
2016: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/27141042/tet-enzymes-are-successively-expressed-during-human-spermatogenesis-and-their-expression-level-is-pivotal-for-male-fertility
#19
Kai Ni, Temuujin Dansranjavin, Nina Rogenhofer, Nihan Oeztuerk, Johanna Deuker, Martin Bergmann, Hans-Christian Schuppe, Florian Wagenlehner, Wolfgang Weidner, Klaus Steger, Undraga Schagdarsurengin
STUDY QUESTION: Are ten-eleven-translocation (TET) 1-3 family enzymes involved in human spermatogenesis and do they impact male fertility? SUMMARY ANSWER: TET1, TET2 and TET3 are successively expressed at different stages of human spermatogenesis, and their expression levels associate with male fertility. WHAT IS KNOWN ALREADY: Spermatogenesis is a complex cell differentiation process accompanied by a drastic epigenetic remodeling. TET1-3 dioxygenases are essential for active DNA demethylation in the paternal pronucleus and in embryonic stem cells...
July 2016: Human Reproduction
https://www.readbyqxmd.com/read/27113584/non-catalytic-roles-for-tet1-protein-negatively-regulating-neuronal-differentiation-through-srgap3-in-neuroblastoma-cells
#20
Jie Gao, Yue Ma, Hua-Lin Fu, Qian Luo, Zhen Wang, Yu-Huan Xiao, Hao Yang, Da-Xiang Cui, Wei-Lin Jin
The methylcytosine dioxygenases TET proteins (TET1, TET2, and TET3) play important regulatory roles in neural function. In this study, we investigated the role of TET proteins in neuronal differentiation using Neuro2a cells as a model. We observed that knockdown of TET1, TET2 or TET3 promoted neuronal differentiation of Neuro2a cells, and their overexpression inhibited VPA (valproic acid)-induced neuronal differentiation, suggesting all three TET proteins negatively regulate neuronal differentiation of Neuro2a cells...
May 2016: Protein & Cell
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