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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
#1
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...
January 11, 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
#2
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...
April 21, 2017: Cell Research
https://www.readbyqxmd.com/read/28426967/an-intrinsic-epigenetic-barrier-for-functional-axon-regeneration
#3
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
#4
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...
April 19, 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
#5
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
#6
Authors 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. This distinct population of cancer stem cells (CSCs)/tumor initiating cells (TICs) 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...
April 4, 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
#7
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...
March 28, 2017: Cellular Reprogramming
https://www.readbyqxmd.com/read/28349832/differential-expression-of-ten-eleven-translocation-genes-in-endometrial-cancers
#8
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
#9
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...
March 21, 2017: EMBO Reports
https://www.readbyqxmd.com/read/28276837/5-hydroxymethylcytosine-5hmc-and-ten-eleven-translocation-1-3-tet1-3-proteins-in-the-dorsal-root-ganglia-of-mouse-expression-and-dynamic-regulation-in-neuropathic-pain
#10
Alexander G Chamessian, Yawar J Qadri, Matthew Cummins, Michele Hendrickson, Temugin Berta, Thomas Buchheit, Thomas Van de Ven
Epigenetic mechanisms are increasingly implicated in chronic pain pathology. In this study, we demonstrate that the novel epigenetic mark 5-hydroxymethylcytosine (5hmC) is present in dorsal root ganglia (DRG) neurons and glia, and its levels increase following nerve injury. Furthermore, we show that the 5hmC-generating Ten-eleven translocation 1-3 (TET1-3) proteins are expressed in a cell-type specific manner in the DRG, with Tet3 displaying differential upregulation after injury, suggesting a potential role in neuropathic pain...
March 1, 2017: Somatosensory & Motor Research
https://www.readbyqxmd.com/read/28229992/increased-5-hydroxymethylcytosine-and-ten-eleven-translocation-protein-expression-in-ultraviolet-b-irradiated-hacat-cells
#11
Dan Wang, Jin-Hua Huang, Qing-Hai Zeng, Can Gu, Shu Ding, Jian-Yun Lu, Jing Chen, Sheng-Bo Yang
BACKGROUND: DNA hydroxymethylation refers to a chemical modification process in which 5-methylcytosine (5mC) is catalyzed to 5- hydroxymethylcytosine (5hmC) by ten-eleven translocation (TET) family proteins. Recent studies have revealed that aberrant TETs expression or 5hmC level may play important roles in the occurrence and development of various pathological and physiological processes including cancer and aging. This study aimed to explore the relation between aberrant DNA hydroxymethylation with skin photoaging and to investigate the levels of TETs, 5mC, and 5hmC expression 24 h after 40 mJ/cm2 and 80 mJ/cm2 doses of ultraviolet B (UVB) irradiation to HaCaT cells...
March 5, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28220892/epigenetic-determinants-of-space-radiation-induced-cognitive-dysfunction
#12
Munjal M Acharya, Al Anoud D Baddour, Takumi Kawashita, Barrett D Allen, Amber R Syage, Thuan H Nguyen, Nicole Yoon, Erich Giedzinski, Liping Yu, Vipan K Parihar, Janet E Baulch
Among the dangers to astronauts engaging in deep space missions such as a Mars expedition is exposure to radiations that put them at risk for severe cognitive dysfunction. These radiation-induced cognitive impairments are accompanied by functional and structural changes including oxidative stress, neuroinflammation, and degradation of neuronal architecture. The molecular mechanisms that dictate CNS function are multifaceted and it is unclear how irradiation induces persistent alterations in the brain. Among those determinants of cognitive function are neuroepigenetic mechanisms that translate radiation responses into altered gene expression and cellular phenotype...
February 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28167661/distinct-roles-for-tet-family-proteins-in-regulating-human-erythropoiesis
#13
Hongxia Yan, Yaomei Wang, Xiaoli Qu, Jie Li, John Hale, Yumin Huang, Chao An, Julien Papoin, Xinhua Guo, Lixiang Chen, Qiaozhen Kang, Wei Li, Vincent P Schulz, Patrick G Gallagher, Christopher D Hillyer, Narla Mohandas, Xiuli An
The ten-eleven translocation (TET) family of proteins plays important roles in a wide range of biological processes by oxidizing 5-methylcytosine (5mC) to 5-hydroxy-methylcytosine. However, their function in erythropoiesis has remained unclear. We show here that TET2 and TET3 but not TET1 are expressed in human erythroid cells, and we explore the role of these proteins in erythropoiesis. Knockdown experiments revealed that TET2 and TET3 have different functions. Suppression of TET3 expression in human CD34(+) cells markedly impaired terminal erythroid differentiation, as reflected by increased apoptosis, the generation of bi/multinucleated polychromatic/orthochromatic erythroblasts, and impaired enucleation, although without effect on erythroid progenitors...
April 6, 2017: Blood
https://www.readbyqxmd.com/read/28111439/ascorbic-acid-increases-demethylation-in-somatic-cell-nuclear-transfer-embryos-of-the-pig-sus-scrofa
#14
Minghui Zhao, Tai-Young Hur, Jingu No, Yoonseok Nam, Hyeunkyu Kim, Gi-Sun Im, Seunghoon Lee
Objective: Investigated the effect and mechanism of ascorbic acid on the development of porcine embryos produced by somatic cell nuclear transfer (SCNT). Methods: Porcine embryos were produced by SCNT and cultured in the presence or absence of ascorbic acid. TET3 in oocytes was knocked down by siRNA injection. After ascorbic acid treatment, reprogramming genes were analyzed by realtime RT-PCR. Furthermore, relative 5mC and 5hmC content in pronuclear were detected by realtime PCR...
January 13, 2017: Asian-Australasian Journal of Animal Sciences
https://www.readbyqxmd.com/read/28069330/top2a-hells-atad2-and-tet3-are-novel-prognostic-markers-in-renal-cell-carcinoma
#15
Dong Chen, Matthias Maruschke, Oliver Hakenberg, Wolfgang Zimmermann, Christian G Stief, Alexander Buchner
OBJECTIVE: To identify and validate novel prognostic marker genes in clear cell renal cell carcinoma (RCC) that are increasingly expressed during tumor progression. METHODS: Total RNA was isolated from normal renal tissue, primary G1 and G3 tumors, 14 samples each, and 32 metastases from RCC patients. Expression profiles were created using oligonucleotide microarrays. Significant gene expression differences (P < .05) were identified among normal kidney, primary tumor, and metastases...
January 6, 2017: Urology
https://www.readbyqxmd.com/read/28043375/comparative-dynamics-of-5-methylcytosine-reprogramming-and-tet-family-expression-during-preimplantation-mammalian-development-in-mouse-and-sheep
#16
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
#17
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
#18
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...
March 2017: Stem Cell Research
https://www.readbyqxmd.com/read/27930333/tet-proteins-influence-the-balance-between-neuroectodermal-and-mesodermal-fate-choice-by-inhibiting-wnt-signaling
#19
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/27918235/comprehensive-mapping-of-5-hydroxymethylcytosine-epigenetic-dynamics-in-axon-regeneration
#20
Yong-Hwee Eddie Loh, Andrew Koemeter-Cox, Mattéa J Finelli, Li Shen, Roland H Friedel, Hongyan Zou
In contrast to central nervous system neurons, dorsal root ganglia (DRG) neurons can switch to a regenerative state after peripheral axotomy. In a screen for chromatin regulators of the regenerative responses in this conditioning lesion paradigm, we identified Tet methylcytosine dioxygenase 3 (Tet3) as upregulated in DRG neurons, along with increased 5-hydroxymethylcytosine (5hmC). We generated genome-wide 5hmC maps in adult DRG, which revealed that peripheral and central axotomy (leading to no regenerative effect) triggered differential 5hmC changes that are associated with distinct signaling pathways...
February 2017: Epigenetics: Official Journal of the DNA Methylation Society
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