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https://www.readbyqxmd.com/read/28211484/regulation-of-mrna-splicing-by-mecp2-via-epigenetic-modifications-in-the-brain
#1
Tian-Lin Cheng, Jingqi Chen, Huida Wan, Bin Tang, Weidong Tian, Lujian Liao, Zilong Qiu
Mutations of X-linked gene Methyl CpG binding protein 2 (MECP2) are the major causes of Rett syndrome (RTT), a severe neurodevelopmental disorder. Duplications of MECP2-containing genomic segments lead to severe autistic symptoms in human. MECP2-coding protein methyl-CpG-binding protein 2 (MeCP2) is involved in transcription regulation, microRNA processing and mRNA splicing. However, molecular mechanisms underlying the involvement of MeCP2 in mRNA splicing in neurons remain largely elusive. In this work we found that the majority of MeCP2-associated proteins are involved in mRNA splicing using mass spectrometry analysis with multiple samples from Mecp2-null rat brain, mouse primary neuron and human cell lines...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28192139/vitamin-c-down-regulate-apo-a-expression-via-tet2-dependent-dna-demethylation-in-hepg2-cells
#2
Kai Qu, Xiao-Feng Ma, Guo-Hua Li, Hai Zhang, Ya-Mi Liu, Kai Zhang, Jun-Fa Zeng, Jian-Jun Lei, Dang-Heng Wei, Zuo Wang
Lipoprotein(a)[Lp(a)] is a risk factor for coronary heart diseases. However, the metabolism of this protein remains poorly understood. Efficient and specific drugs that can decrease high plasma levels of Lp(a) have not been developed yet. Vitamin C is responsible for maintaining the catalytic activity of a group of iron and 2-oxoglutarate (2OG)-dependent dioxygenases and induces the generation of 5-hydroxymethylcytosine (5hmC) via Ten-eleven translocation (Tet) dioxygenases. In addition, It has been reported vitamin C deficiency induces atherosclerosis and increases Lp(a) and apo(a) plasma levels in Lp(a)+ mice...
February 10, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28167661/distinct-roles-for-tet-family-proteins-in-regulating-human-erythropoiesis
#3
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 TET family of proteins plays important roles in a wide range of biological processes by oxidizing 5-methylcytosine (5mC) to 5-hydroxy-methylcytosine (5hmC). 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, generation of bi/multinucleated polychromatic/orthochromatic erythroblasts and impaired enucleation, though without effect on erythroid progenitors...
February 6, 2017: Blood
https://www.readbyqxmd.com/read/28141796/epigenomic-landscape-of-5-hydroxymethylcytosine-reveals-its-transcriptional-regulation-of-lncrnas-in-colorectal-cancer
#4
Hanyang Hu, Maoguo Shu, Lin He, Xueyuan Yu, Xiangyu Liu, Yalin Lu, Yinghong Chen, Xiaoping Miao, Xiaohua Chen
BACKGROUND: DNA methylation at the 5 position of cytosine (5mC) can be converted to 5-hydroxymethylcytosine (5hmC) by the ten-eleven translocation family. The loss of global levels of 5hmC has been regarded as a hallmark in various cancers. 5-hydroxymethylcytosine is distributed at protein-coding gene bodies and promoters; however, the role and distribution of 5hmC at long non-coding RNAs (lncRNAs) is not clear. We investigated the distribution and regulatory roles of 5hmC for lncRNAs in colorectal cancer (CRC)...
January 31, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28130252/a-tet2-dnmt1-complex-prevents-abnormal-dna-methylation
#5
(no author information available yet)
Oxidative stress targets TET2 and DNMT1 to chromatin to increase both DNA methylation and 5hmC.
January 27, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28130236/h-o-ta-estimation-of-dna-methylation-and-hydroxylation-levels-and-efficiencies-from-time-course-data
#6
Charalampos Kyriakopoulos, Pascal Giehr, Verena Wolf
MOTIVATION: Methylation and hydroxylation of cytosines to form 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) belong to the most important epigenetic modifications and their vital role in the regulation of gene expression has been widely recognized. Recent experimental techniques allow to infer methylation and hydroxylation levels at CpG dinucleotides but require a sophisticated statistical analysis to achieve accurate estimates. RESULTS: We present H(O)TA, a software tool based on a stochastic modeling approach, which simultaneously analyzes time course data from hairpin bisulfite sequencing and hairpin oxidative bisulfite sequencing...
January 27, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28128679/early-life-stress-links-5-hydroxymethylcytosine-to-anxiety-related-behaviors
#7
Ligia A Papale, Andy Madrid, Sisi Li, Reid S Alisch
Environmental stress contributes to the development of psychiatric disorders, including post-traumatic stress disorder and anxiety. While even acute stress alters gene expression, the molecular mechanisms underlying these changes remain largely unknown. 5-hydroxymethylcytosine (5hmC) is a novel environmentally sensitive DNA modification that is highly enriched in the brain and is associated with active transcription of neuronal genes. Here we examined behavioral and molecular alterations in adult mice that experienced an early-life stress prior to weaning (postnatal day 12 to 18) and found anxiety-like behaviors in adult female mice that were accompanied by correlated disruptions of hypothalamic 5hmC and gene expression in 118 genes, revealing potentially functional 5hmC (i...
January 27, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28125731/correlated-5-hydroxymethylcytosine-5hmc-and-gene-expression-profiles-underpin-gene-and-organ-specific-epigenetic-regulation-in-adult-mouse-brain-and-liver
#8
I-Hsuan Lin, Yi-Fan Chen, Ming-Ta Hsu
BACKGROUND: DNA methylation is an epigenetic mechanism essential for gene regulation and vital for mammalian development. 5-hydroxymethylcytosine (5hmC) is the first oxidative product of the TET-mediated 5-methylcytosine (5mC) demethylation pathway. Aside from being a key intermediate in cytosine demethylation, 5hmC may have potential regulatory functions with emerging importance in mammalian biology. METHODS: Here, we investigate the global 5hmC enrichment in five brain structures, including cerebellum, cerebral cortex, hippocampus, hypothalamus and thalamus, as well as liver tissues from female and male adult mice by using chemical capture-based technique coupled with next-generation sequencing...
2017: PloS One
https://www.readbyqxmd.com/read/28125717/epigenetic-alterations-affecting-transcription-factors-and-signaling-pathways-in-stromal-cells-of-endometriosis
#9
Iveta Yotova, Emily Hsu, Catherine Do, Aulona Gaba, Matthias Sczabolcs, Sabine Dekan, Lukas Kenner, Rene Wenzl, Benjamin Tycko
Endometriosis is characterized by growth of endometrial-like tissue outside the uterine cavity. Since its pathogenesis may involve epigenetic changes, we used Illumina 450K Methylation Beadchips to profile CpG methylation in endometriosis stromal cells compared to stromal cells from normal endometrium. We validated and extended the Beadchip data using bisulfite sequencing (bis-seq), and analyzed differential methylation (DM) at the CpG-level and by an element-level classification for groups of CpGs in chromatin domains...
2017: PloS One
https://www.readbyqxmd.com/read/28124145/role-of-oxidative-stress-in-epigenetic-modification-of-mmp-9-promoter-in-the-development-of-diabetic-retinopathy
#10
Renu A Kowluru, Yang Shan
BACKGROUND: In the pathogenesis of diabetic retinopathy, damaged retinal mitochondria accelerate apoptosis of retinal capillary cells, and regulation of oxidative stress by manipulating mitochondrial superoxide dismutase (SOD2) protects mitochondrial homeostasis and prevents the development of diabetic retinopathy. Diabetes also activates matrix metalloproteinase-9 (MMP-9), and activated MMP-9 damages retinal mitochondria. Recent studies have shown a dynamic DNA methylation process playing an important role in regulation of retinal MMP-9 transcription in diabetes; the aim of this study is to investigate the role of oxidative stress in MMP-9 transcription...
January 25, 2017: Graefe's Archive for Clinical and Experimental Ophthalmology
https://www.readbyqxmd.com/read/28115522/the-5-hydroxymethylcytosine-5hmc-reader-uhrf2-is-required-for-normal-levels-of-5hmc-in-mouse-adult-brain-and-spatial-learning-and-memory
#11
Ruoyu Chen, Qiao Zhang, Xiaoya Duan, Philippe York, Guo-Dong Chen, Pengcheng Yin, Haijun Zhu, Meichen Xu, Peilin Chen, Qihan Wu, Dali Li, Jacques Samarut, Guoliang Xu, Pumin Zhang, Xiaohua Cao, Jiwen Li, Jiemin Wong
UHRF2 has been implicated as a novel regulator for both DNA methylation (5mC) and hydroxymethylation (5hmC), but its physiological function and role in DNA methylation/hydroxymethylation are unknown. Here we show that in mice Uhrf2 is more abundantly expressed in the brain and a few other tissues. Uhrf2 knockout mice are viable, fertile and exhibit no gross defect. Although there is no significant change of DNA methylation, the Uhrf2 null mice exhibit a reduction of 5hmC in the brain including cortex and hippocampus...
January 23, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28115151/tetrachloro-1-4-benzoquinone-induces-apoptosis-of-mouse-embryonic-stem-cells
#12
Cuiping Li, Fengbang Wang, Hailin Wang
Pentachlorophenol (PCP) is a widespread, persistent environmental contaminant, and it is enzymatically activated to form a reactive metabolite, tetrachloro-1,4-benzoquinone (TCBQ). To our knowledge, there is no information about TCBQ toxicity on embryonic stem cells. Here, we demonstrated that TCBQ induced significantly apoptosis of mouse embryonic stem cells in a concentration-dependent manner. We also showed that TCBQ elevated genomic 5-hydroxymethylcytosine (5hmC) by affecting ten-eleven translocation (Tet) dioxygenases in mouse embryonic stem cells...
January 2017: Journal of Environmental Sciences (China)
https://www.readbyqxmd.com/read/28111439/ascorbic-acid-increases-demethylation-in-somatic-cell-nuclear-transfer-embryos-of-the-pig-sus-scrofa
#13
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/28107650/acetylation-enhances-tet2-function-in-protecting-against-abnormal-dna-methylation-during-oxidative-stress
#14
Yang W Zhang, Zhihong Wang, Wenbing Xie, Yi Cai, Limin Xia, Hariharan Easwaran, Jianjun Luo, Ray-Whay Chiu Yen, Yana Li, Stephen B Baylin
TET proteins, by converting 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), are hypothesized, but not directly shown, to protect promoter CpG islands (CGIs) against abnormal DNA methylation (DNAm) in cancer. We define such a protective role linked to DNA damage from oxidative stress (OS) known to induce this abnormality. TET2 removes aberrant DNAm during OS through interacting with DNA methyltransferases (DNMTs) in a "Yin-Yang" complex targeted to chromatin and enhanced by p300 mediated TET2 acetylation...
January 19, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28063323/genetic-and-epigenetic-regulation-on-the-transcription-of-gabrb2-genotype-dependent-hydroxymethylation-and-methylation-alterations-in-schizophrenia
#15
Lu Zong, Lin Zhou, Yu Hou, Lulu Zhang, Wei Jiang, Wenwei Zhang, Lijuan Wang, Xia Luo, Shiqing Wang, Cong Deng, Zhizhen Peng, Shufen Li, Jiming Hu, Hu Zhao, Cunyou Zhao
To improve our understanding of the abnormalities and non-Mendelian inheritance characteristics of schizophrenia, this study examined DNA methylation (5mC) and hydroxymethylation (5hmC) in the schizophrenia-associated GABRB2 gene encoding the type A γ-aminobutyric acid receptor β2 subunit. DNAs from the peripheral white blood cells of 279 schizophrenic patients and 256 controls from the Chinese Han population were examined to reveal that the GABRB2 promoter P1-5mC level which was correlated with olanzapine administration, P2-5mC/5hmC level, and Alu-5mC level which was correlated with administration of ziprasidone or oxcarbazepine, were increased in schizophrenic patients...
December 28, 2016: Journal of Psychiatric Research
https://www.readbyqxmd.com/read/28052262/neil3-dependent-regulation-of-cardiac-fibroblast-proliferation-prevents-myocardial-rupture
#16
Maria B Olsen, Gunn A Hildrestrand, Katja Scheffler, Leif Erik Vinge, Katrine Alfsnes, Vuk Palibrk, Junbai Wang, Christine G Neurauter, Luisa Luna, Jostein Johansen, Jonas D S Øgaard, Ingrid K Ohm, Geir Slupphaug, Anna Kuśnierczyk, Arnt E Fiane, Sverre-Henning Brorson, Lili Zhang, Lars Gullestad, William E Louch, Per Ole Iversen, Ingunn Østlie, Arne Klungland, Geir Christensen, Ivar Sjaastad, Pål Sætrom, Arne Yndestad, Pål Aukrust, Magnar Bjørås, Alexandra V Finsen
Myocardial infarction (MI) triggers a reparative response involving fibroblast proliferation and differentiation driving extracellular matrix modulation necessary to form a stabilizing scar. Recently, it was shown that a genetic variant of the base excision repair enzyme NEIL3 was associated with increased risk of MI in humans. Here, we report elevated myocardial NEIL3 expression in heart failure patients and marked myocardial upregulation of Neil3 after MI in mice, especially in a fibroblast-enriched cell fraction...
January 3, 2017: Cell Reports
https://www.readbyqxmd.com/read/28043375/comparative-dynamics-of-5-methylcytosine-reprogramming-and-tet-family-expression-during-preimplantation-mammalian-development-in-mouse-and-sheep
#17
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/28040665/spectroscopic-quantification-of-5-hydroxymethylcytosine-in-genomic-dna-using-boric-acid-functionalized-nano-microsphere-fluorescent-probes
#18
Hua-Yan Chen, Jing-Ru Wei, Jiong-Xiu Pan, Wei Zhang, Fu-Quan Dang, Zhi-Qi Zhang, Jing Zhang
5-hydroxymethylcytosine (5hmC) is the sixth base of DNA. It is involved in active DNA demethylation and can be a marker of diseases such as cancer. In this study, we developed a simple and sensitive 2-(4-boronophenyl)quinoline-4-carboxylic acid modified poly (glycidyl methacrylate (PBAQA-PGMA) fluorescent probe to detect the 5hmC content of genomic DNA based on T4 β-glucosyltransferase-catalyzed glucosylation of 5hmC. The fluorescence-enhanced intensity recorded from the DNA sample was proportional to its 5-hydroxymethylcytosine content and could be quantified by fluorescence spectrophotometry...
December 16, 2016: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/28039446/5-hydroxymethylcytosine-correlates-with-epigenetic-regulatory-mutations-but-may-not-have-prognostic-value-in-predicting-survival-in-normal-karyotype-acute-myeloid-leukemia
#19
Jae-Sook Ahn, Hyeoung-Joon Kim, Yeo-Kyeoung Kim, Seung-Shin Lee, Seo-Yeon Ahn, Sung-Hoon Jung, Deok-Hwan Yang, Je-Jung Lee, Hee Jeong Park, Seung Hyun Choi, Chul Won Jung, Jun-Ho Jang, Hee Je Kim, Joon Ho Moon, Sang Kyun Sohn, Jong-Ho Won, Sung-Hyun Kim, Szardenings Michael, Mark D Minden, Dennis Dong Hwan Kim
Stem cells display remarkably high levels of 5-hydroxymethylcytosine (5hmC). Both TET2 and IDH1/2 mutations can impair the production of 5hmC, thus decreasing 5hmC levels. TET2 or IDH1/2 mutations are commonly observed in acute myeloid leukemia (AML). However, the implications of 5hmC on survival in normal karyotype AML patients have not been fully evaluated. The 5hmC levels were analyzed in 375 patients using ELISA. The levels of 5hmC in DNA samples were converted to a log scale for the analysis and correlations with TET2 and/or IDH1/2 mutations were evaluated...
January 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28030787/dna-demethylation-mediated-by-down-regulated-tets-in-the-testes-of%C3%A2-rare-minnow-gobiocypris-rarus-under-bisphenol-a-exposure
#20
Cong Yuan, Yingying Zhang, Yan Liu, Song Wang, Zaizhao Wang
Inevitable BPA exposure resulted in disturbance of DNA methylation status and our published study suspected that BPA has the potentiality to disturb DNA demethylation and GSH production in Gobiocypris rarus testes. To confirm this conjecture, several experiments were carried out in the present study. Adult male G. rarus was exposed to 1, 15 and 225 μg L(-1) (nominal concentration) BPA for two weeks. The levels of 5-methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC), glutathione (GSH), and enzyme levels for DNA methylation and GSH synthesis in the testes were detected...
December 21, 2016: Chemosphere
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