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5 hydroxymethylcytosine

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https://www.readbyqxmd.com/read/29924591/epigenetic-optical-mapping-of-5-hydroxymethylcytosine-in-nanochannel-arrays
#1
Tslil Gabrieli, Hila Sharim, Gil Nifker, Jonathan Jeffet, Tamar Shahal, Rani Arielly, Michal Levy-Sakin, Lily Hoch, Nissim Arbib, Yael Michaeli, Yuval Ebenstein
The epigenetic mark 5-hydroxymethylcytosine (5-hmC) is a distinct product of active DNA demethylation that is linked to gene regulation, development, and disease. In particular, 5-hmC levels dramatically decline in many cancers, potentially serving as an epigenetic biomarker. The noise associated with next-generation 5-hmC sequencing hinders reliable analysis of low 5-hmC containing tissues such as blood and malignant tumors. Additionally, genome-wide 5-hmC profiles generated by short-read sequencing are limited in providing long-range epigenetic information relevant to highly variable genomic regions, such as the 3...
June 20, 2018: ACS Nano
https://www.readbyqxmd.com/read/29912180/an-alternative-culture-method-to-maintain-genomic-hypomethylation-of-mouse-embryonic-stem-cells-using-mek-inhibitor-pd0325901-and-vitamin-c
#2
Cuiping Li, Weiyi Lai, Hailin Wang
Embryonic stem (ES) cells have the potential to differentiate into any of the three germ layers (endoderm, mesoderm, or ectoderm), and can generate many lineages for regenerative medicine. ES cell culture in vitro has long been the subject of widespread concerns. Classically, mouse ES cells are maintained in serum and leukemia inhibitory factor (LIF)-containing medium. However, under serum/LIF conditions, cells show heterogeneity in morphology and the expression profile of pluripotency-related genes, and are mostly in a metastable state...
June 1, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29908294/tet2-regulates-osteoclast-differentiation-by-interacting-with-runx1-and-maintaining-genomic-5-hydroxymethylcytosine-5hmc
#3
Yajing Chu, Zhigang Zhao, David Wayne Sant, Ganqian Zhu, Sarah M Greenblatt, Lin Liu, Jinhuan Wang, Zeng Cao, Jeanette Cheng Tho, Shi Chen, Xiaochen Liu, Peng Zhang, Jaroslaw P Maciejewski, Stephen Nimer, Gaofeng Wang, Weiping Yuan, Feng-Chun Yang, Mingjiang Xu
As a dioxygenase, Ten-eleven translocation 2 (TET2) catalyzes subsequent steps of 5-methylcytosine (5mC) oxidation. Tet2 plays a critical role in the self-renewal, proliferation, and differentiation of hematopoietic stem cells, but its impact on mature hematopoietic cells is not well-characterized. Here we show that Tet2 plays an essential role in osteoclastogenesis. Deletion of Tet2 impairs the differentiation of osteoclast precursor cells (macrophages) and their maturation into bone-resorbing osteoclasts in vitro...
June 13, 2018: Genomics, Proteomics & Bioinformatics
https://www.readbyqxmd.com/read/29894742/association-of-high-5-hydroxymethylcytosine-levels-with-ten-eleven-translocation-2-overexpression-and-inflammation-in-sj%C3%A3-gren-s-syndrome-patients
#4
Carolina Lagos, Patricia Carvajal, Isabel Castro, Daniela Jara, Sergio González, Sergio Aguilera, María-José Barrera, Andrew F G Quest, Verónica Bahamondes, Claudio Molina, Ulises Urzúa, Marcela A Hermoso, Cecilia Leyton, María-Julieta González
Here, we determined the 5-hydroxymethylcytosine (5hmC), 5-methylcytosine (5mC), Ten Eleven Translocation (TETs), and DNA methyltransferases (DNMTs) levels in epithelial and inflammatory cells of labial salivary glands (LSG) from Sjögren's syndrome (SS)-patients and the effect of cytokines on HSG cells. LSG from SS-patients, controls and HSG cells incubated with cytokines were analysed. Levels of 5mC, 5hmC, DNMTs, TET2 and MeCP2 were assessed by immunofluorescence. In epithelial cells from SS-patients, an increase in TET2, 5hmC and a decrease in 5mC and MeCP2 were observed, additionally, high levels of 5mC and DNMTs and low levels of 5hmC were detected in inflammatory cells...
June 9, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/29878202/loss-of-5hmc-identifies-a-new-type-of-aberrant-dna-hypermethylation-in-glioma
#5
Agustin F Fernandez, Gustavo F Bayón, Marta I Sierra, Rocio G Urdinguio, Estela G Toraño, Maria García, Antonella Carella, Virginia Lopez, Pablo Santamarina, Raúl F Pérez, Thalía Belmonte, Juan Ramon Tejedor, Isabel Cobo, Pablo Menendez, Cristina Mangas, Cecilia Ferrero, Luis Rodrigo, Aurora Astudillo, Ignacio Ortea, Sergio Cueto Díaz, Pablo Rodríguez-Gonzalez, J Ignacio García Alonso, Manuela Mollejo, Bárbara Meléndez, Gemma Dominguez, Felix Bonilla, Mario F Fraga
Aberrant DNA hypermethylation is a hallmark of cancer although the underlying molecular mechanisms are still poorly understood. To study the possible role of 5-hydroxymethylcytosine (5hmC) in this process we analyzed the global and locus-specific genome-wide levels of 5hmC and 5mC in human primary samples from 12 non-tumoral brains and 53 gliomas. We found that the levels of 5hmC identified in non-tumoral samples were significantly reduced in gliomas. Strikingly, hypo-hydroxymethylation at 4,627 (9.3%) CpG sites was associated with aberrant DNA hypermethylation and was strongly enriched in CpG island (CGI) shores...
June 5, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29862069/effects-of-5-hydroxymethylcytosine-epigenetic-modification-on-the-stability-and-molecular-recognition-of-vegf-i-motif-and-g-quadruplex-structures
#6
Rhianna K Morgan, Michael M Molnar, Harshul Batra, Bethany Summerford, Randy M Wadkins, Tracy A Brooks
Promoters often contain asymmetric G- and C-rich strands, in which the cytosines are prone to epigenetic modification via methylation (5-mC) and 5-hydroxymethylation (5-hmC). These sequences can also form four-stranded G-quadruplex (G4) or i-motif (iM) secondary structures. Although the requisite sequences for epigenetic modulation and iM/G4 formation are similar and can overlap, they are unlikely to coexist. Despite 5-hmC being an oxidization product of 5-mC, the two modified bases cluster at distinct loci...
2018: Journal of Nucleic Acids
https://www.readbyqxmd.com/read/29858571/tet1-and-tet2-maintain-mesenchymal-stem-cell-homeostasis-via-demethylation-of-the-p2rx7-promoter
#7
Ruili Yang, Tingting Yu, Xiaoxing Kou, Xiang Gao, Chider Chen, Dawei Liu, Yanheng Zhou, Songtao Shi
Ten-eleven translocation (Tet) family-mediated DNA oxidation represents an epigenetic modification capable of converting 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC), which regulates various biological processes. However, it is unknown whether Tet family affects mesenchymal stem cells (MSCs) or the skeletal system. Here we show that depletion of Tet1 and Tet2 results in impaired self-renewal and differentiation of bone marrow MSCs (BMMSCs) and a significant osteopenia phenotype. Tet1 and Tet2 deficiency reduces demethylation of the P2rX7 promoter and downregulates exosome release, leading to intracellular accumulation of miR-297a-5p, miR-297b-5p, and miR-297c-5p...
June 1, 2018: Nature Communications
https://www.readbyqxmd.com/read/29803640/loss-of-5-hydroxymethylcytosine-is-an-epigenetic-biomarker-in-cutaneous-t-cell-lymphoma
#8
Lei Qiu, Fengjie Liu, Shengguo Yi, Xueying Li, Xiaoqing Liu, Cheng Xiao, Christine Guo Lian, Ping Tu, Yang Wang
DNA hydroxymethylation at the 5 position of cytosine (5-hmC) is a product of the ten-eleven translocation (TET) family of DNA hydroxylases. Accumulating evidence shows that loss of 5-hmC is critical for various biological and pathological processes. However, its level in cutaneous T cell lymphoma remains largely unknown. Here we report that the loss of 5-hmC is an epigenetic hallmark of cutaneous T cell lymphoma (CTCL), with diagnostic and prognostic implications. Immunohistochemistry staining on 90 mycosis fungoides (MF) cases demonstrated a significant decrease of 5-hmC staining in CD4+ T cells in patch and tumor stages, especially in MF-LCT, compared to benign inflammatory dermatoses...
May 24, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29797259/genome-wide-mapping-of-methylated-and-hydroxyl-methylated-cytosines-using-a-modified-hpaii-tiny-fragment-enrichment-by-ligation-mediated-pcr-tagged-sequencing-protocol
#9
Sanchari Battachariyya, Ruslana Tytarenko, Christoph Heuck, John Greally, Amit Verma
Here we describe a method for genome wide investigation of methylation and hydroxymethylation status of cytosines. This protocol is an improvement of the HELP-tagging protocol previously described by Suzuki et al. It involves the glucosylation of 5-hydroxymethylcytosines (5-hmC) with β-glucosyl transferase (β-GT), thus rendering them resistant to digestion by MspI. Parallel digestion of β-GT treated samples with MspI, untreated sample with MspI and another untreated sample with HpaII, followed by adapter ligation, parallel sequencing and bioinformatics processing results in a differential display of MspI digestion sites that allows the determination of the distribution of 5-methylcytosines (5-mC) and 5-hmC at these sites...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29791079/overexpression-of-tet3-in-donor-cells-enhances-goat-somatic-cell-nuclear-transfer-efficiency
#10
Chengquan Han, Ruizhi Deng, Tingchao Mao, Yan Luo, Biao Wei, Peng Meng, Lu Zhao, Qing Zhang, Fusheng Quan, Liu Jun, Yong Zhang
Ten-eleven translocation 3 (TET3) mediates active DNA demethylation of paternal genomes during mouse embryonic development. However, the mechanism of DNA demethylation in goat embryos remains unknown. In addition, aberrant DNA methylation reprogramming prevalently occurs in cloned embryos by somatic cell nuclear transfer (SCNT). In this study, we reported that TET3 is a key factor in DNA demethylation in goat pre-implantation embryos. Knockdown of Tet3 hindered DNA demethylation at 2-4-cell stage in goat embryos and decreased Nanog expression in blastocysts...
May 23, 2018: FEBS Journal
https://www.readbyqxmd.com/read/29790956/5-hydroxymethylcytosine-alterations-in-the-human-postmortem-brains-of-autism-spectrum-disorder
#11
Ying Cheng, Ziyi Li, Sasicha Manupipatpong, Li Lin, Xuekun Li, Tianlei Xu, Yong-Hui Jiang, Qiang Shu, Hao Wu, Peng Jin
Autism spectrum disorders (ASD) include a group of syndromes characterized by impaired language, social, and communication skills, in addition to restrictive behaviors or stereotypes. However, with a prevalence of 1.5% in developed countries and high comorbidity rates, no clear underlying mechanism that unifies the heterogeneous phenotypes of ASD exists. 5-hydroxymethylcytosine (5hmC) is highly enriched in the brain and recognized as an essential epigenetic mark in developmental and brain disorders. To explore the role of 5hmC in ASD, we used the genomic DNA isolated from the postmortem cerebellum of both ASD patients and age-matched controls to profile genome-wide distribution of 5hmC...
May 22, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29786565/modelling-non-alcoholic-fatty-liver-disease-in-human-hepatocyte-like-cells
#12
Marcus J Lyall, Jessy Cartier, John P Thomson, Kate Cameron, Jose Meseguer-Ripolles, Eoghan O'Duibhir, Dagmara Szkolnicka, Baltasar Lucendo Villarin, Yu Wang, Giovanny Rodriguez Blanco, Warwick B Dunn, Richard R Meehan, David C Hay, Amanda J Drake
Non-alcoholic fatty liver disease (NAFLD) is the most common cause of liver disease in developed countries. An in vitro NAFLD model would permit mechanistic studies and enable high-throughput therapeutic screening. While hepatic cancer-derived cell lines are a convenient, renewable resource, their genomic, epigenomic and functional alterations mean their utility in NAFLD modelling is unclear. Additionally, the epigenetic mark 5-hydroxymethylcytosine (5hmC), a cell lineage identifier, is rapidly lost during cell culture, alongside expression of the Ten-eleven-translocation ( TET ) methylcytosine dioxygenase enzymes, restricting meaningful epigenetic analysis...
July 5, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29773648/ten-eleven-translocation-2-demethylates-the-mmp9-promoter-and-its-down-regulation-in-preeclampsia-impairs-trophoblast-migration-and-invasion
#13
Xiaoliang Li, Chunlian Wu, Ying Shen, Ke Wang, Li Tang, Mi Zhou, Ming Yang, Tianying Pan, Xinghui Liu, Wenming Xu
Preeclampsia is the most common clinical disorder in pregnancy and might result from disordered uterine environments caused by epigenetic modifications, including deregulation of DNA methylation/demethylation. Recent research has indicated that 5-hydroxymethylcytosine (5hmC), a DNA base derived from 5-methylcytosine (5mC) via oxidation by ten-eleven translocation (TET) enzymes, is involved in DNA methylation-related plasticity. Here, we report that TET2 expression and 5hmC abundance are significantly altered in the placentas from preeclampsia patients...
May 17, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29772230/replacing-c189-in-the-bzip-domain-of-zta-with-s-t-v-or-a-changes-dna-binding-specificity-to-four-types-of-double-stranded-dna
#14
Sreejana Ray, Desiree Tillo, Nima Assad, Aniekanabasi Ufot, Christopher Deppmann, Stewart R Durell, Aleksey Porollo, Charles Vinson
Zta is a bZIP transcription factor (TF) in the Epstein-Barr virus that binds unmethylated and methylated DNA sequences. Substitution of cysteine 189 of Zta to serine (Zta(C189S)) results in a virus that is unable to execute the lytic cycle which was attributed to a change in binding to methylated DNA sequences. To learn more about the role of this position in defining sequence-specific DNA binding, we mutated cysteine 189 to four other amino acids producing Zta(C189S), Zta(C189T), Zta(C189A), and Zta(C189V) mutants...
May 14, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29757674/eicosapentaenoic-acid-induces-dna-demethylation-in-carcinoma-cells-through-a-tet1-dependent-mechanism
#15
Veronica Ceccarelli, Virginia Valentini, Simona Ronchetti, Lorenza Cannarile, Monia Billi, Carlo Riccardi, Laura Ottini, Vincenzo Nicola Talesa, Francesco Grignani, Alba Vecchini
In cancer cells, global genomic hypomethylation is found together with localized hypermethylation of CpG islands within the promoters and regulatory regions of silenced tumor suppressor genes. Demethylating agents may reverse hypermethylation, thus promoting gene re-expression. Unfortunately, demethylating strategies are not efficient in solid tumor cells. DNA demethylation is mediated by ten-eleven translocation enzymes (TETs). They sequentially convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), which is associated with active transcription; 5-formylcytosine; and finally, 5-carboxylcytosine...
May 14, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29747586/selective-modulation-of-local-linkages-between-active-transcription-and-oxidative-demethylation-activity-shapes-cardiomyocyte-specific-gene-body-epigenetic-status-in-mice
#16
Mayumi Oda, Shunichi Wakabayashi, N Ari Wijetunga, Shinsuke Yuasa, Hirokazu Enomoto, Ruri Kaneda, Sung Han Yoon, Nishant Mittal, Qiang Jing, Masako Suzuki, John M Greally, Keiichi Fukuda, Shinji Makino
BACKGROUND: Cell-type-specific genes exhibit heterogeneity in genomic contexts and may be subject to different epigenetic regulations through different gene transcriptional processes depending on the cell type involved. The gene-body regions (GBRs) of some cardiomyocyte (CM)-specific genes are long and highly hypomethylated in CMs. To explore the cell-type specificities of epigenetic patterns and functions, multiple epigenetic modifications of GBRs were compared among CMs, liver cells and embryonic stem cells (ESCs)...
May 10, 2018: BMC Genomics
https://www.readbyqxmd.com/read/29743892/epigenetic-regulations-in-neural-stem-cells-and-neurological-diseases
#17
REVIEW
Hang Zhou, Bin Wang, Hao Sun, Xingshun Xu, Yongxiang Wang
Among the regulatory mechanisms of the renewal and differentiation of neural stem cells, recent evidences support that epigenetic modifications such as DNA methylation, histone modification, and noncoding RNAs play critical roles in the regulation on the proliferation and differentiation of neural stem cells. In this review, we discussed recent advances of DNA modifications on the regulative mechanisms of neural stem cells. Among these epigenetic modifications, DNA 5-hydroxymethylcytosine (5hmC) modification is emerging as an important modulator on the proliferation and differentiation of neural stem cells...
2018: Stem Cells International
https://www.readbyqxmd.com/read/29735542/pml-recruits-tet2-to-regulate-dna-modification-and-cell-proliferation-in-response-to-chemotherapeutic-agent
#18
Chengli Song, Lina Wang, Xiaoyan Wu, Kai Wang, Dan Xie, Qi Xiao, Songyu Li, Kui Jiang, Lujian Liao, John R Yates, Jiing-Dwan Lee, Qingkai Yang
Aberrant DNA methylation plays a critical role in the development and progression of cancer. Failure to demethylate and to consequently reactivate methylation-silenced genes in cancer contributes to chemotherapeutic resistance, yet the regulatory mechanisms of DNA demethylation in response to chemotherapeutic agents remain unclear. Here, we show that promyelocytic leukemia (PML) recruits ten-eleven translocation dioxygenase 2 (TET2) to regulate DNA modification and cell proliferation in response to chemotherapeutic agents...
May 7, 2018: Cancer Research
https://www.readbyqxmd.com/read/29732371/hippocampal-tet1-and-tet2-expression-and-dna-hydroxymethylation-are-affected-by-physical-exercise-in-aged-mice
#19
Peter Jessop, Maria Toledo-Rodriguez
The function of 5-hydroxymethylcytosine (5hmC) is poorly understood. 5hmC is an epigenetic modification of DNA, resulting from the oxidation of 5-methylcytosine (5mC) by the Fe2+ , and 2-oxoglutarate-dependent, 10-11 translocation methylcytosine dioxygenases (TET1, TET2, and TET3). Recent evidence suggests that, in addition to being an intermediate in active demethylation, 5hmC may also have an epigenetic role. 5hmC is enriched in the adult brain, where it has been implicated in regulating neurogenesis. The rate of adult neurogenesis decreases with age, however physical exercise has been shown to counteract this deficit...
2018: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/29713349/the-dynamic-dna-demethylation-during-postnatal-neuronal-development-and-neural-stem-cell-differentiation
#20
Huikang Tao, Pei Xie, Yuhang Cao, Liqi Shu, Liping Li, Junchen Chen, Guangfeng Tian, Yingliang Zhuang, Qiang Shu, Xuekun Li
Background: DNA demethylation, the conversion of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC), plays important roles in diverse biological processes and multiple diseases by regulating gene expression. Methods: In this study, utilizing DNA dot blot, immunofluorescence staining, and qRT-PCR, we studied the expression pattern of Tets, the enzymes governing DNA demethylation, and the levels of 5hmC, 5fC, and 5caC during the postnatal neuronal development of mice...
2018: Stem Cells International
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