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https://www.readbyqxmd.com/read/28918013/mir-135b-stimulates-osteosarcoma-recurrence-and-lung-metastasis-via-notch-and-wnt-%C3%AE-catenin-signaling
#1
Hua Jin, Song Luo, Yun Wang, Chang Liu, Zhenghao Piao, Meng Xu, Wei Guan, Qing Li, Hua Zou, Qun-You Tan, Zhen-Zhou Yang, Yan Wang, Dong Wang, Cheng-Xiong Xu
Cancer stem cells (CSCs) play an important role in osteosarcoma (OS) metastasis and recurrence, and both Wnt/β-catenin and Notch signaling are essential for the development of the biological traits of CSCs. However, the mechanism that underlies the simultaneous hyperactivation of both Wnt/β-catenin and Notch signaling in OS remains unclear. Here, we report that expression of miR-135b correlates with the overall and recurrence-free survival of OS patients, and that miR-135b has an activating effect on both Wnt/β-catenin and Notch signaling...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28870206/3-6-dihydroxyflavone-regulates-microrna-34a-through-dna-methylation
#2
Xiaoli Peng, Hui Chang, Junli Chen, Qianyong Zhang, Xiaoping Yu, Mantian Mi
BACKGROUND: Breast cancer is the common cancer in China. In previous study, we determined that 3,6-dihydroxyflavone (3,6-DHF) increases miR-34a significantly in breast carcinogenesis, but the mechanism remains unclear. METHODS: We used qRT-PCR to analyze miR-34a and ten-eleven translocation (TET)1, TET2, TET3 levels in breast cancer cells. With a cellular breast carcinogenesis model and an experimental model of carcinogenesis in rats, TET1 levels were evaluated by western blot analysis and immunofluorescence...
September 5, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28842817/methamphetamine-induces-tet1-and-tet3-dependent-dna-hydroxymethylation-of-crh-and-avp-genes-in-the-rat-nucleus-accumbens
#3
Subramaniam Jayanthi, Betina Gonzalez, Michael T McCoy, Bruce Ladenheim, Veronica Bisagno, Jean Lud Cadet
Methamphetamine (METH) addiction is a biopsychosocial disorder that is accompanied by multiple relapses even after prolonged abstinence, suggesting the possibilities of long-lasting maladaptive epigenetic changes in the brain. Here, we show that METH administration produced time-dependent increases in the expression of corticotropin-releasing hormone (Crh/Crf), arginine vasopressin (Avp), and cocaine- and amphetamine-regulated transcript prepropeptide (Cartpt) mRNAs in the rat nucleus accumbens (NAc). Chromatin immunoprecipitation (ChIP) assays revealed that METH increased the abundance of phosphorylated CREB (pCREB) at the promoter of Cartpt but not at Avp or Crh DNA sequences...
August 25, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28745936/5-hydroxymethylcytosine-in-dna-repair-a-new-player-or-a-red-herring
#4
Omar L Kantidze, Sergey V Razin
Active DNA demethylation performed by ten-eleven translocation (TET) enzymes produces 5-hydroxymethylcytosines, 5-formylcytosines, and 5-carboxylcytosines. Recent observations suggest that 5-hydroxymethylcytosine is a stable epigenetic mark rather than merely an intermediate of DNA demethylation. However, the clear functional role of this new epigenetic player is elusive. The contribution of 5-hydroxymethylation to DNA repair is being discussed currently. Recently, Jiang and colleagues have demonstrated that DNA damage response-activated ATR kinase phosphorylates TET3 in mammalian cells and promotes DNA demethylation and 5-hydroxymethylcytosine accumulation...
August 18, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28716910/methylcytosine-dioxygenase-tet3-interacts-with-thyroid-hormone-nuclear-receptors-and-stabilizes-their-association-to-chromatin
#5
Wenyue Guan, Romain Guyot, Jacques Samarut, Frédéric Flamant, Jiemin Wong, Karine Cécile Gauthier
Thyroid hormone receptors (TRs) are members of the nuclear hormone receptor superfamily that act as ligand-dependent transcription factors. Here we identified the ten-eleven translocation protein 3 (TET3) as a TR interacting protein increasing cell sensitivity to T3. The interaction between TET3 and TRs is independent of TET3 catalytic activity and specifically allows the stabilization of TRs on chromatin. We provide evidence that TET3 is required for TR stability, efficient binding of target genes, and transcriptional activation...
August 1, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28710961/epigenetic-modification-differences-between-fetal-fibroblast-cells-and-mesenchymal-stem-cells-of-the-arbas-cashmere-goat
#6
Xiao Wang, Zhimin Wang, Qing Wang, Hefei Wang, Hao Liang, Dongjun Liu
To explore the epigenetic mechanisms regulating mesenchymal stem cells, we analyzed epigenetic patterns in control goat fetal fibroblast cells (gFFCs), adipose-derived stem cells (gADSCs), bone marrow stromal cells (gBMSCs), and muscle-derived satellite cells (gMDSCs). We found that the 5mC content of gBMSC genomes was lower than that of gFFC genomes, while the 5mC content of gADSC and gMDSC genomes surpassed that of gFFC genomes. H3K9 acetylation did not differ significantly among those cells; gFFCs, gADSCs, and gMDSCs contained acetylated H3K9, H3K14, H3K18, H4K5, and H4K12, but gBMSCs contained almost no acetylated H4K5 and H4K12...
July 9, 2017: Research in Veterinary Science
https://www.readbyqxmd.com/read/28521490/transcript-levels-of-ten-eleven-translocation-type-1-3-in-cervical-cancer-and-non-cancerous-cervical-tissues
#7
Dorota Ewa Bronowicka-Kłys, Andrzej Roszak, Piotr Pawlik, Stefan Sajdak, Anna Sowińska, Paweł Piotr Jagodziński
Decreased expression of ten-eleven translocation (TET1, TET2 and TET3) proteins has been reported in various types of cancer. However, the expression levels of TET proteins in cervical cancer (CC) remain to be elucidated. The present study determined the levels of TET1, TET2 and TET3 transcripts in cancerous (n=80) and non-cancerous cervical tissues (n=41). The results revealed a significant reduction in TET1 transcripts (P=0.0000001) in cervical tissue samples from patients with primary CC compared with samples from control patients...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28504700/lineage-specific-functions-of-tet1-in-the-postimplantation-mouse-embryo
#8
Rita Khoueiry, Abhishek Sohni, Bernard Thienpont, Xinlong Luo, Joris Vande Velde, Michela Bartoccetti, Bram Boeckx, An Zwijsen, Anjana Rao, Diether Lambrechts, Kian Peng Koh
The mammalian TET enzymes catalyze DNA demethylation. While they have been intensely studied as major epigenetic regulators, little is known about their physiological roles and the extent of functional redundancy following embryo implantation. Here we define non-redundant roles for TET1 at an early postimplantation stage of the mouse embryo, when its paralogs Tet2 and Tet3 are not detectably expressed. TET1 regulates numerous genes defining differentiation programs in the epiblast and extraembryonic ectoderm...
July 2017: Nature Genetics
https://www.readbyqxmd.com/read/28465359/elevated-foxg1-and-sox2-in-glioblastoma-enforces-neural-stem-cell-identity-through-transcriptional-control-of-cell-cycle-and-epigenetic-regulators
#9
Harry Bulstrode, Ewan Johnstone, Maria Angeles Marques-Torrejon, Kirsty M Ferguson, Raul Bardini Bressan, Carla Blin, Vivien Grant, Sabine Gogolok, Ester Gangoso, Sladjana Gagrica, Christine Ender, Vassiliki Fotaki, Duncan Sproul, Paul Bertone, Steven M Pollard
Glioblastoma multiforme (GBM) is an aggressive brain tumor driven by cells with hallmarks of neural stem (NS) cells. GBM stem cells frequently express high levels of the transcription factors FOXG1 and SOX2. Here we show that increased expression of these factors restricts astrocyte differentiation and can trigger dedifferentiation to a proliferative NS cell state. Transcriptional targets include cell cycle and epigenetic regulators (e.g., Foxo3, Plk1, Mycn, Dnmt1, Dnmt3b, and Tet3). Foxo3 is a critical repressed downstream effector that is controlled via a conserved FOXG1/SOX2-bound cis-regulatory element...
April 15, 2017: Genes & Development
https://www.readbyqxmd.com/read/28452984/frequent-somatic-mutations-in-epigenetic-regulators-in-newly-diagnosed-chronic-myeloid-leukemia
#10
E Togasaki, J Takeda, K Yoshida, Y Shiozawa, M Takeuchi, M Oshima, A Saraya, A Iwama, K Yokote, E Sakaida, C Hirase, A Takeshita, K Imai, H Okumura, Y Morishita, N Usui, N Takahashi, S Fujisawa, Y Shiraishi, K Chiba, H Tanaka, H Kiyoi, K Ohnishi, S Ohtake, N Asou, Y Kobayashi, Y Miyazaki, S Miyano, S Ogawa, I Matsumura, C Nakaseko, T Naoe
Although tyrosine kinase inhibitors (TKIs) have significantly improved the prognosis of chronic myeloid leukemia (CML), the ability of TKIs to eradicate CML remains uncertain and patients must continue TKI therapy for indefinite periods. In this study, we performed whole-exome sequencing to identify somatic mutations in 24 patients with newly diagnosed chronic phase CML who were registered in the JALSG CML212 study. We identified 191 somatic mutations other than the BCR-ABL1 fusion gene (median 8, range 1-17)...
April 28, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28449087/methyl-cpg-binding-domain-protein-1-regulates-localization-and-activity-of-tet1-in-a-cxxc3-domain-dependent-manner
#11
Peng Zhang, Cathia Rausch, Florian D Hastert, Boyana Boneva, Alina Filatova, Sujit J Patil, Ulrike A Nuber, Yu Gao, Xinyu Zhao, M Cristina Cardoso
Cytosine modifications diversify and structure the genome thereby controlling proper development and differentiation. Here, we focus on the interplay of the 5-methylcytosine reader Mbd1 and modifier Tet1 by analyzing their dynamic subcellular localization and the formation of the Tet oxidation product 5-hydroxymethylcytosine in mammalian cells. Our results demonstrate that Mbd1 enhances Tet1-mediated 5-methylcytosine oxidation. We show that this is due to enhancing the localization of Tet1, but not of Tet2 and Tet3 at heterochromatic DNA...
July 7, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28433419/disconnect-between-alcohol-induced-alterations-in-chromatin-structure-and-gene-transcription-in-a-mouse-embryonic-stem-cell-model-of-exposure
#12
Kylee J Veazey, Haiqing Wang, Yudhishtar S Bedi, William M Skiles, Richard Cheng-An Chang, Michael C Golding
Alterations to chromatin structure induced by environmental insults have become an attractive explanation for the persistence of exposure effects into subsequent life stages. However, a growing body of work examining the epigenetic impact that alcohol and other drugs of abuse exert consistently notes a disconnection between induced changes in chromatin structure and patterns of gene transcription. Thus, an important question is whether perturbations in the 'histone code' induced by prenatal exposures to alcohol implicitly subvert gene expression, or whether the hierarchy of cellular signaling networks driving development is such that they retain control over the transcriptional program...
May 2017: Alcohol
https://www.readbyqxmd.com/read/28429771/crispr-cas9-mediated-genome-editing-in-one-blastomere-of-two-cell-embryos-reveals-a-novel-tet3-function-in-regulating-neocortical-development
#13
Lingbo Wang, Min-Yin Li, Chao Qu, Wan-Ying Miao, Qi Yin, Jiaoyang Liao, Hua-Teng Cao, Min Huang, Kai Wang, Erwei Zuo, Guangdun Peng, Shu-Xin Zhang, Guodong Chen, Qing Li, Ke Tang, Qian Yu, Zhoujie Li, Catherine Cl Wong, Guoliang Xu, Naihe Jing, Xiang Yu, Jinsong Li
Studying the early function of essential genes is an important and challenging problem in developmental biology. Here, we established a method for rapidly inducing CRISPR-Cas9-mediated mutations in one blastomere of two-cell stage embryos, termed 2-cell embryo-CRISPR-Cas9 injection (2CC), to study the in vivo function of essential (or unknown) genes in founder chimeric mice. By injecting both Cre mRNA and CRISPR-Cas9 targeting the gene of interest into fluorescent reporter mice, the 2CC method can trace both wild-type and mutant cells at different developmental stages, offering internal control for phenotypic analyses of mutant cells...
June 2017: Cell Research
https://www.readbyqxmd.com/read/28426967/an-intrinsic-epigenetic-barrier-for-functional-axon-regeneration
#14
Yi-Lan Weng, Ran An, Jessica Cassin, Jessica Joseph, Ruifa Mi, Chen Wang, Chun Zhong, Seung-Gi Jin, Gerd P Pfeifer, Alfonso Bellacosa, Xinzhong Dong, Ahmet Hoke, Zhigang He, Hongjun Song, Guo-Li Ming
Mature neurons in the adult peripheral nervous system can effectively switch from a dormant state with little axonal growth to robust axon regeneration upon injury. The mechanisms by which injury unlocks mature neurons' intrinsic axonal growth competence are not well understood. Here, we show that peripheral sciatic nerve lesion in adult mice leads to elevated levels of Tet3 and 5-hydroxylmethylcytosine in dorsal root ganglion (DRG) neurons. Functionally, Tet3 is required for robust axon regeneration of DRG neurons and behavioral recovery...
April 19, 2017: Neuron
https://www.readbyqxmd.com/read/28422379/increased-5-hydroxymethylation-levels-in-the-hippocampus-of-rat-extinguished-from-cocaine-self-administration
#15
Anna Sadakierska-Chudy, Małgorzata Frankowska, Karolina Wydra, Joanna Jastrzębska, Joanna Miszkiel, Małgorzata Filip
Drug craving and relapse risk during abstinence from cocaine are thought to be caused by persistent changes in transcription and chromatin regulation. Although several brain regions are involved in these processes, the hippocampus seems to play an important role in context-evoked craving and drug-seeking behavior. Only a few studies have examined epigenetic alterations during a period of cocaine abstinence. To investigate the effects of cocaine abstinence on DNA methylation and gene expression, rats that self-administered the drug underwent cocaine abstinence in two time points with extinction training...
July 2017: Hippocampus
https://www.readbyqxmd.com/read/28409505/dynamic-changes-in-dna-demethylation-in-the-tree-shrew-tupaia-belangeri-chinensis-brain-during-postnatal-development-and-aging
#16
Shu Wei, Hai-Rong Hua, Qian-Quan Chen, Ying Zhang, Fei Chen, Shu-Qing Li, Fan Li, Jia-Li Li
Brain development and aging are associated with alterations in multiple epigenetic systems, including DNA methylation and demethylation patterns. Here, we observed that the levels of the 5-hydroxymethylcytosine (5hmC) ten-eleven translocation (TET) enzyme-mediated active DNA demethylation products were dynamically changed and involved in postnatal brain development and aging in tree shrews (Tupaia belangeri chinensis). The levels of 5hmC in multiple anatomic structures showed a gradual increase throughout postnatal development, whereas a significant decrease in 5hmC was found in several brain regions in aged tree shrews, including in the prefrontal cortex and hippocampus, but not the cerebellum...
March 18, 2017: Zoological Research
https://www.readbyqxmd.com/read/28376560/hypoxia-mediated-epigenetic-regulation-of-stemness-in-brain-tumor-cells
#17
Pankaj Prasad, Shivani Arora Mittal, Jonita Chongtham, Sujata Mohanty, Tapasya Srivastava
Activation of pluripotency regulatory circuit is an important event in solid tumor progression and the hypoxic microenvironment is known to enhance the stemness feature of some cells. The distinct population of cancer stem cells (CSCs)/tumor initiating cells exist in a niche and augment invasion, metastasis, and drug resistance. Previously, studies have reported global hypomethylation and site-specific aberrant methylation in gliomas along with other epigenetic modifications as important contributors to genomic instability during glioma progression...
June 2017: Stem Cells
https://www.readbyqxmd.com/read/28350187/epigenetic-status-of-h19-igf2-imprinted-genes-and-loss-of-5-hydroxymethylcytosine-in-the-brain-of-cloned-goats
#18
Mingtian Deng, Caifang Ren, Zifei Liu, Guomin Zhang, Feng Wang, Yongjie Wan
In mammals, the imprinted genes play vital roles in development and are generally controlled by DNA methylation at imprinting control regions (ICRs). Recently, it was discovered that 5-hydroxymethylcytosine (5-hmC) is a stable epigenetic modification; however, its functions in cloned animal genomes have not yet been fully elucidated. In this study, we interrogated and quantified the 5-hmC levels in the brain of cloned goats and discovered upregulation of Uhrf1 (p < 0.001), Dnmt1 (p < 0.05), Dnmt3a (p < 0...
June 2017: Cellular Reprogramming
https://www.readbyqxmd.com/read/28349832/differential-expression-of-ten-eleven-translocation-genes-in-endometrial-cancers
#19
Piotr Ciesielski, Paweł Jóźwiak, Katarzyna Wójcik-Krowiranda, Ewa Forma, Łukasz Cwonda, Sylwia Szczepaniec, Andrzej Bieńkiewicz, Magdalena Bryś, Anna Krześlak
Ten-eleven translocation proteins are α-ketoglutarate-dependent dioxygenases involved in the conversion of 5-methylcytosines (5-mC) to 5-hydroxymethylcytosine (5-hmC), 5-formylcytosine, and 5-carboxylcytosine that play a significant role in DNA demethylation. Deregulation of TET genes expression and changes in the level of 5-hmC are thought to be associated with the onset and progression of several types of cancer, but there are no such data related to endometrial cancer. The aim of the work was to investigate the messenger RNA expression levels of TET1, TET2, and TET3 in relation to clinicopathological characteristics of endometrial cancer as well as the correlation between expression of TET genes and the level of 5-hmC/5-mC...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28325772/tet3-mediated-dna-oxidation-promotes-atr-dependent-dna-damage-response
#20
Dewei Jiang, Shu Wei, Fei Chen, Ying Zhang, Jiali Li
An efficient, accurate, and timely DNA damage response (DDR) is crucial for the maintenance of genome integrity. Here, we report that ten-eleven translocation dioxygenase (TET) 3-mediated conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) in response to ATR-dependent DDR regulates DNA repair. ATR-dependent DDR leads to dynamic changes in 5hmC levels and TET3 enzymatic activity. We show that TET3 is an ATR kinase target that oxidizes DNA during ATR-dependent DNA damage repair. Modulation of TET3 expression and activity affects DNA damage signaling and DNA repair and consequently cell death...
May 2017: EMBO Reports
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