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active DNA demethylation

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https://www.readbyqxmd.com/read/28077417/aid-is-a-key-regulator-of-myeloid-erythroid-differentiation-and-dna-methylation-in-hematopoietic-stem-progenitor-cells
#1
Hiroyoshi Kunimoto, Anna Sophia McKenney, Cem Meydan, Kaitlyn Shank, Abbas Nazir, Franck Rapaport, Benjamin Durham, Francine E Garrett-Bakelman, Elodie Pronier, Alan H Shih, Ari Melnick, Jayanta Chaudhuri, Ross L Levine
Recent studies have reported activation-induced cytidine deaminase (AID) and ten-eleven-translocation (TET) family members regulate active DNA demethylation. Genetic alterations of TET2 occur in myeloid malignancies and hematopoietic specific loss of Tet2 induces aberrant hematopoietic stem cell (HSC) self-renewal/differentiation, implicating TET2 as a master regulator of normal and malignant hematopoiesis. Despite the functional link between AID and TET in epigenetic gene regulation, the role of AID loss in hematopoiesis and myeloid transformation remains to be investigated...
January 11, 2017: Blood
https://www.readbyqxmd.com/read/28058582/genome-wide-dna-methylation-patterns-analysis-of-noncoding-rnas-in-temporal-lobe-epilepsy-patients
#2
Wenbiao Xiao, Yuze Cao, Hongyu Long, Zhaohui Luo, Shuyu Li, Na Deng, Jianjian Wang, Xiaoyan Lu, Tianfeng Wang, Shangwei Ning, Lihua Wang, Bo Xiao
Temporal lobe epilepsy (TLE) is the most common form of adult epilepsy and frequently evolving drug resistance. Although there is growing consensus that noncoding ribonucleic acids (ncRNAs) are modulators of TLE, the knowledge about the deoxyribonucleic acid (DNA) methylation patterns of ncRNAs in TLE remains limited. In the current study, we constructed DNA methylation profiles from 30 TLE patients and 30 healthy controls for ncRNAs, primarily focusing on long ncRNAs (lncRNAs) and microRNAs (miRNAs), by reannotating data of DNA methylation BeadChip...
January 5, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28057213/a-new-molecular-mechanism-underlying-the-antitumor-effect-of-dna-methylation-inhibitors-via-an-antiviral-immune-response
#3
Y Saito, T Nakaoka, H Saito
Chromatin remodeling mediated by DNA methylation and histone modifications play critical roles in the transcriptional regulation of protein-coding genes, noncoding RNAs such as microRNAs, and endogenous retroviruses (ERVs). Many studies have shown that aberrant DNA methylation and histone modifications are associated with the initiation and progression of various malignancies. Epigenetic silencing of tumor suppressor genes in cancer is generally mediated by DNA hypermethylation of CpG island promoters and histone modifications such as histone deacetylation, methylation of histone H3 lysine 9 (H3K9), and trimethylation of H3K27...
2017: Advances in Protein Chemistry and Structural Biology
https://www.readbyqxmd.com/read/28051879/wnt5a-promoter-methylation-is-associated-with-better-responses-and-longer-progression-free-survival-in-colorectal-cancer-patients-treated-with-5-fluorouracil-based-chemotherapy
#4
Guozhong Jiang, Jiangxin Lin, Weiwei Wang, Miaomiao Sun, Kuisheng Chen, Feng Wang
BACKGROUND: Aberrant activation of the canonical WNT or WNT/β-catenin signaling pathway plays a pivotal role in multiple types of cancers. WNT5A, a nontransforming WNT protein suppressing the Wnt/β-catenin signaling pathway, is frequently detected to be hypermethylated in colorectal cancer (CRC). In this study, we investigated the prognostic value of WNT5A methylation in human patients and its potential underlying molecular mechanisms in cultured human CRC cells. METHODS: We measured WNT5A mRNA level using qRT-PCR and DNA methylation using methylation-specific PCR (MSP) in HCT116, HT29, SW620, HCT8, LoVo, SW480, and Rko CRC cells...
January 4, 2017: Genetic Testing and Molecular Biomarkers
https://www.readbyqxmd.com/read/28043375/comparative-dynamics-of-5-methylcytosine-reprogramming-and-tet-family-expression-during-preimplantation-mammalian-development-in-mouse-and-sheep
#5
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
#6
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/28040665/spectroscopic-quantification-of-5-hydroxymethylcytosine-in-genomic-dna-using-boric-acid-functionalized-nano-microsphere-fluorescent-probes
#7
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/28038351/microrna-29-impairs-the-early-phase-of-reprogramming-process-by-targeting-active-dna-demethylation-enzymes-and-wnt-signaling
#8
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...
December 19, 2016: Stem Cell Research
https://www.readbyqxmd.com/read/28035374/activation-of-oncogenic-pathways-in-classical-hodgkin-lymphoma-by-decitabine-a-rationale-for-combination-with-small-molecular-weight-inhibitors
#9
Tatjana Maria Swerev, Thomas Wirth, Alexey Ushmorov
DNA methylation is an epigenetic control mechanism that contributes to the specific phenotype and to the oncogenic program of virtually all tumor entities. Although efficacy of demethylating agents in classical Hodgkin lymphoma (cHL) was not specifically tested, a case of regression of relapsed metastatic cHL was described as a fortunate side‑effect of the demethylating agent 5‑azacytidine in a patient with myelodysplastic syndrome. We investigated molecular mechanisms of decitabine (5‑Aza‑dC) antitumor activity in cHL using gene expression profiling followed by gene set enrichment analysis...
December 30, 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/28032024/urinary-measurement-of-epigenetic-dna-modifications-a-non-invasive-assessment-of-the-whole-body-epigenetic-status-in-healthy-subjects-and-colorectal-cancer-patients
#10
Rafal Rozalski, Daniel Gackowski, Agnieszka Siomek-Gorecka, Zbigniew Banaszkiewicz, Ryszard Olinski
Active mechanism of DNA demethylation can be responsible for the activation of previously silenced genes. Products of 5-methylcytosine oxidation are released into the bloodstream and eventually excreted with urine. Therefore, whole-body epigenetic status can be assessed non-invasively on the basis of the urinary excretion of a broad spectrum of epigenetic modifications: 5-hydroxymethylcytosine (5-hmCyt), 5-formylcytosine (5-fCyt), 5-carboxycytosine (5-caCyt), and 5-hydroxymethyluracil (5-hmUra). We have developed a specific and sensitive, isotope-dilution, automated, online, two-dimensional ultra-performance liquid chromatography system with tandem mass spectrometry (2D UPLC-MS/MS) to measure 5-hmCyt, 5-fCyt, 5-caCyt, and their deoxynucleosides in the same urine sample...
December 2016: ChemistryOpen
https://www.readbyqxmd.com/read/28026094/phenotypic-characteristics-of-aged-cd4-cd28-null-t-lymphocytes-are-determined-by-changes-in-the-whole-genome-dna-methylation-pattern
#11
Beatriz Suarez-Álvarez, Ramón M Rodríguez, Karin Schlangen, Aroa Baragaño Raneros, Leonardo Márquez-Kisinousky, Agustín F Fernández, Carmen Díaz-Corte, Ana M Aransay, Carlos López-Larrea
Aging is associated with a progressive loss of the CD28 costimulatory molecule in CD4(+) lymphocytes (CD28(null) T cells), which is accompanied by the acquisition of new biological and functional properties that give rise to an impaired immune response. The regulatory mechanisms that govern the appearance and function of this cell subset during aging and in several associated inflammatory disorders remain controversial. Here, we present the whole-genome DNA methylation and gene expression profiles of CD28(null) T cells and its CD28(+) counterpart...
December 27, 2016: Aging Cell
https://www.readbyqxmd.com/read/28003999/synergistic-cytotoxic-effect-of-l-asparaginase-combined-with-decitabine-as-a-demethylating-agent-in-pediatric-t-all-with-specific-epigenetic-signature
#12
Salvatore Serravalle, Salvatore N Bertuccio, Annalisa Astolfi, Fraia Melchionda, Andrea Pession
T-Acute Lymphoblastic Leukemia (T-ALL) remains a subgroup of pediatric ALL, with a lower response to standard chemotherapy. Some recent studies established the fundamental role of epigenetic aberrations such as DNA hypermethylation, to influence patients' outcome and response to chemotherapy. Moreover, L-asparaginase is an important chemotherapeutic agent for treatment of ALL and resistance to this drug has been linked to ASNS expression, which can be silenced through methylation. Therefore, we tested whether the sensitivity of T-ALL cell lines towards L-asparaginase is correlated to the epigenetic status of ASNS gene and whether the sensitivity can be modified by concurrent demethylating treatment...
2016: BioMed Research International
https://www.readbyqxmd.com/read/28003489/restricted-tet2-expression-in-germinal-center-type-b-cells-promotes-stringent-epstein-barr-virus-latency
#13
Coral K Wille, Yangguang Li, Lixin Rui, Eric C Johannsen, Shannon C Kenney
: EBV latently infects normal B cells, and contributes to the development of certain human lymphomas. Newly infected B cells support a highly transforming form (type III) of viral latency; however, long-term EBV infection in immunocompetent hosts is limited to B cells with a more restricted form of latency (type I) where most viral gene expression is silenced by promoter DNA methylation. How EBV converts latency type is unclear, although it is known that type I latency is associated with germinal center (GC) B cell phenotype, and type III latency with an activated B-cell (ABC) phenotype...
December 21, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27998022/the-effects-of-the-dna-methyltranfserases-inhibitor-5-azacitidine-on-ageing-oxidative-stress-and-dna-methylation-of-adipose-derived-stem-cells
#14
Katarzyna Kornicka, Krzysztof Marycz, Monika Marędziak, Krzysztof A Tomaszewski, Jakub Nicpoń
Human adipose tissue is a great source of adult mesenchymal stem cells (MSCs) which are recognized from their ability to self-renew and differentiation into multiple lineages. MSCs have promised a vast therapeutic potential in treatment many diseases including tissue injury and immune disorders. However, their regenerative potential profoundly depends on patients' age. Age-related deterioration of MSC is associated with cellular senescence mainly caused by increased DNA methylation status, accumulation of oxidative stress factors and mitochondria dysfunction...
December 20, 2016: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/27993162/tet-enzymes-double-agents-in-the-transposable-element-host-genome-conflict
#15
Patricia Gerdes, Sandra R Richardson, Geoffrey J Faulkner
The mouse genome is replete with retrotransposon sequences, from evolutionarily young elements with mutagenic potential that must be controlled, to inactive molecular fossils whose sequences can be domesticated over evolutionary time to benefit the host genome. In an exciting new study, de la Rica and colleagues have uncovered a complex relationship between ten-eleven translocation (TET) proteins and retrotransposons in mouse embryonic stem cells (ESCs), implicating TETs as enhancers in the exaptation and function of retroelement sequences...
December 20, 2016: Genome Biology
https://www.readbyqxmd.com/read/27989104/dna-demethylation-of-the-foxp3-enhancer-is-maintained-through-modulation-of-ten-eleven-translocation-and-dna-methyltransferases
#16
Varun Sasidharan Nair, Mi Hye Song, Myunggon Ko, Kwon Ik Oh
Stable expression of Foxp3 is ensured by demethylation of CpG motifs in the Foxp3 intronic element, the conserved non-coding sequence 2 (CNS2), which persists throughout the lifespan of regulatory T cells (Tregs). However, little is known about the mechanisms on how CNS2 demethylation is sustained. In this study, we found that Ten-Eleven-Translocation (Tet) DNA dioxygenase protects the CpG motifs of CNS2 from re-methylation by DNA methyltransferases (Dnmts) and prevents Tregs from losing Foxp3 expression under inflammatory conditions...
December 2016: Molecules and Cells
https://www.readbyqxmd.com/read/27984131/enhanced-photo-geno-toxicity-of-demethylated-chlorpromazine-metabolites
#17
Fabrizio Palumbo, Guillermo Garcia-Lainez, Daniel Limones-Herrero, M Dolores Coloma, Javier Escobar, M Consuelo Jiménez, Miguel A Miranda, Inmaculada Andreu
Chlorpromazine (CPZ) is an anti-psychotic drug widely used to treat disorders such as schizophrenia or manic-depression. Unfortunately, CPZ exhibits undesirable side effects such as phototoxic and photoallergic reactions in humans. In general, the influence of drug metabolism on this type of these reactions has not been previously considered in photosafety testing. Thus, the present work aims to investigate the possible photo(geno)toxic potential of drug metabolites, using CPZ as an established reference compound...
October 27, 2016: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/27978466/metabolite-identification-of-bentysrepinine-y101-a-novel-anti-hbv-agent-in-rats-using-a-five-step-strategy-based-on-a-combined-workflow-with-two-different-platforms-of-liquid-chromatography-tandem-mass-spectrometry
#18
Huirong Fan, Zhanxing Hu, Ruixing Li, Shiqi Dong, Yuan Gu, Ting Liu, Duanyun Si, Guangyi Liang, Changxiao Liu
Bentysrepinine (Y101), a derivative of repensine (a compound isolated from Dichondrarepens Forst), is a novel phenyalanine dipeptide inhibiting DNA-HBV and cccDNA activities and is currently under development for the treatment of hepatitis B virus (HBV)-infected hepatitis. Our previous study implied that there might be an existence of extensive metabolism of Y101 in rats. Therefore, it is necessary to perform metabolic profiling study to further evaluate its safety and drug-like properties. In this study, the metabolism of Y101 in rats was investigated by a convincible five-step strategy to characterize metabolites in plasma and that excreted into urine, bile and feces...
January 1, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/27974453/epigenetic-networks-regulate-the-transcriptional-program-in-memory-and-terminally-differentiated-cd8-t-cells
#19
Ramon M Rodriguez, Beatriz Suarez-Alvarez, José L Lavín, David Mosén-Ansorena, Aroa Baragaño Raneros, Leonardo Márquez-Kisinousky, Ana M Aransay, Carlos Lopez-Larrea
Epigenetic mechanisms play a critical role during differentiation of T cells by contributing to the formation of stable and heritable transcriptional patterns. To better understand the mechanisms of memory maintenance in CD8(+) T cells, we performed genome-wide analysis of DNA methylation, histone marking (acetylated lysine 9 in histone H3 and trimethylated lysine 9 in histone), and gene-expression profiles in naive, effector memory (EM), and terminally differentiated EM (TEMRA) cells. Our results indicate that DNA demethylation and histone acetylation are coordinated to generate the transcriptional program associated with memory cells...
December 14, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27956642/dna-demethylation-is-initiated-in-the-central-cells-of-arabidopsis-and-rice
#20
Kyunghyuk Park, M Yvonne Kim, Martin Vickers, Jin-Sup Park, Youbong Hyun, Takashi Okamoto, Daniel Zilberman, Robert L Fischer, Xiaoqi Feng, Yeonhee Choi, Stefan Scholten
Cytosine methylation is a DNA modification with important regulatory functions in eukaryotes. In flowering plants, sexual reproduction is accompanied by extensive DNA demethylation, which is required for proper gene expression in the endosperm, a nutritive extraembryonic seed tissue. Endosperm arises from a fusion of a sperm cell carried in the pollen and a female central cell. Endosperm DNA demethylation is observed specifically on the chromosomes inherited from the central cell in Arabidopsis thaliana, rice, and maize, and requires the DEMETER DNA demethylase in Arabidopsis DEMETER is expressed in the central cell before fertilization, suggesting that endosperm demethylation patterns are inherited from the central cell...
December 27, 2016: Proceedings of the National Academy of Sciences of the United States of America
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