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DNA demethylation

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https://www.readbyqxmd.com/read/28098352/dna-repair-and-erasure-of-5-methylcytosine-in-vertebrates
#1
Lars Schomacher, Christof Niehrs
DNA methylation plays important roles in development and disease. Yet, only recently has the dynamic nature of this epigenetic mark via oxidation and DNA repair-mediated demethylation been recognized. A major conceptual challenge to the model that DNA methylation is reversible is the risk of genomic instability, which may come with widespread DNA repair activity. Here, we focus on recent advances in mechanisms of TET-TDG mediated demethylation and cellular strategies that avoid genomic instability. We highlight the recently discovered involvement of NEIL DNA glycosylases, which cooperate with TDG in oxidative demethylation to accelerate substrate turnover and promote the organized handover of harmful repair intermediates to maintain genome stability...
January 18, 2017: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/28090275/induction-of-epigenetic-alteration-by-cpuk02-an-ent-kaurenoid-derivative-of-stevioside
#2
Pooneh Mokarram, Zeinab Mohammadi, Saeid Khazayel, Zhang Dayong
BACKGROUND: Dietary polyphenols, such as those found in green tea and red wine, are linked to antitumor activity. They are known to influence many signaling pathways epigenetically within the human body. In this regard, CPUK02 (15-Oxosteviol benzyl ester) is a new ent-kaurenoid derivative of stevioside and exhibits strong anti-cancer activity in vitro and in vivo. Nowadays, the role of epigenetics in cancer has been the subject of intensive study and DNA methylation targeting represents a relevant strategy for cancer treatment...
January 2017: Avicenna Journal of Medical Biotechnology
https://www.readbyqxmd.com/read/28089213/a-genome-wide-profiling-of-brain-dna-hydroxymethylation-in-alzheimer-s-disease
#3
Jinying Zhao, Yun Zhu, Jingyun Yang, Lin Li, Hao Wu, Philip L De Jager, Peng Jin, David A Bennett
INTRODUCTION: DNA methylation is a key epigenetic mechanism in brain aging and Alzheimer's disease (AD). The newly discovered 5-hydroxymethylcytosine mediates DNA demethylation, is highly abundant in the brain, and is dynamically regulated by life experiences. However, little is known about its genome-wide patterns and potential role in AD. METHODS: Using a genome-wide capture followed by high-throughput sequencing, we studied the genome-wide distribution of 5-hydroxymethylcytosine at specific genomic loci in human AD brain and identified differentially hydroxymethylated regions (DhMRs) associated with AD pathology...
January 6, 2017: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/28077801/human-papillomavirus-type-16-e6-suppresses-microrna-23b-expression-in-human-cervical-cancer-cells-through-dna-methylation-of-the-host-gene-c9orf3
#4
Chi Lam Au Yeung, Tsun Yee Tsang, Pak Lun Yau, Tim Tak Kwok
Oncogenic protein E6 of human papillomavirus type 16 (HPV-16) is believed to involve in the aberrant methylation in cervical cancer as it upregulates DNA methyltransferase 1 (DNMT1) through tumor suppressor p53. In addition, DNA demethylating agent induces the expression of one of the HPV-16 E6 regulated microRNAs (miRs), miR-23b, in human cervical carcinoma SiHa cells. Thus, the importance of DNA methylation and miR-23b in HPV-16 E6 associated cervical cancer development is investigated. In the present study, however, it is found that miR-23b is not embedded in any typical CpG island...
6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28077417/aid-is-a-key-regulator-of-myeloid-erythroid-differentiation-and-dna-methylation-in-hematopoietic-stem-progenitor-cells
#5
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/28074931/eid3-directly-associates-with-dnmt3a-during-transdifferentiation-of-human-umbilical-cord-mesenchymal-stem-cells-to-npc-like-cells
#6
Liang Luo, Wen-Jin Chen, James Q Yin, Ru-Xiang Xu
There has been recently been increased interest in the plasticity of human umbilical cord mesenchymal stem cells (UMSCs) and their potential in the treatment of neurological disorders. In this study, UMSCs were transdifferentiated into neural stem-like cells (uNSCL), these cells grow in neurosphere-like structures and express high levels of NSCs markers. Epigenetics-related gene screening was here used to assess the relationship between E1A-like inhibitor of differentiation 3 (EID3), a p300 inhibitor, and DNA methyltransferase 3 A (DNMT3A) during the transdifferentiation of UMSCs into uNSCL in vitro...
January 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28059831/effect-of-dihydroartemisinin-on-uhrf1-gene-expression-in-human-prostate-cancer-pc-3-cells
#7
Shijuan Du, Ge Xu, Wenqin Zou, Tingxiu Xiang, Ziguo Luo
As the second most common cancer in men around the world, prostate cancer is increasingly gaining more attention. Dihydroartemisinin (DHA) has been proven to be a promising anticancer agent in vitro as well as in vivo in accumulating data. However, the detailed mechanisms of how DHA action in human prostate cancer PC-3 cells remain elusive. This study aimed to investigate the effects of DHA, a novel anticancer agent, by inhibiting the expression of ubiquitin like containing PHD and ring finger 1 (UHRF1) in PC-3 cells...
January 2, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28059468/gene-expression-analysis-combined-with-functional-genomics-approach-identifies-itih5-as-tumor-suppressor-gene-in-cervical-carcinogenesis
#8
Jessica Dittmann, Angelique Ziegfeld, Lars Jansen, Mieczyslaw Gajda, Vera Kloten, Edgar Dahl, Ingo B Runnebaum, Matthias Dürst, Claudia Backsch
Progression from human papillomavirus-induced premalignant cervical intraepithelial neoplasia (CIN) to cervical cancer (CC) is driven by genetic and epigenetic events. Our microarray-based expression study has previously shown that inter-α-trypsin-inhibitor heavy chain 5 (ITIH5) mRNA levels in CCs were significantly lower than in high-grade precursor lesions (CIN3s). Therefore, we aimed to analyze in depth ITIH5 expression during cervical carcinogenesis in biopsy material and cell culture. Moreover, functional analyses were performed by ectopic expression of ITIH5 in different cell lines...
January 6, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28058582/genome-wide-dna-methylation-patterns-analysis-of-noncoding-rnas-in-temporal-lobe-epilepsy-patients
#9
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
#10
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/28057015/downregulation-of-long-noncoding-rna-meg3-is-associated-with-poor-prognosis-and-promoter-hypermethylation-in-cervical-cancer
#11
Jun Zhang, Zhongqiu Lin, Yali Gao, Tingting Yao
BACKGROUND: Our previous study reported that MEG3 is an important tumor suppressor gene that is inactivated in cervical cancer. However, the diagnostic and prognostic values of MEG3, as well as the molecular mechanism of MEG3 inactivation in cervical cancer, remain unclear. In this study, we aimed to further elucidate the role and potential inactivation mechanism of MEG3 in cervical cancer. METHODS: ROC curve and Cox regression analyses were used to assess the diagnostic and prognostic value of MEG3 in patients with cervical cancer...
January 5, 2017: Journal of Experimental & Clinical Cancer Research: CR
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
#12
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
#13
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
#14
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
#15
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/28039450/aberrant-promoter-methylation-of-hogg1-may-be-associated-with-increased-risk-of-non-small-cell-lung-cancer
#16
Hualong Qin, Jianjie Zhu, Yuanyuan Zeng, Wenwen Du, Dan Shen, Zhe Lei, Qian Qian, Jian-An Huang, Zeyi Liu
DNA methylation may epigenetically inactivate tumor suppressor genes in NSCLC. As the human 8-oxoguanine DNA glycosylase (hOGG1) gene promoter is frequently methylated in NSCLC, we evaluated whether genetic or epigenetic alterations of hOGG1 are associated with increased risk of non-small cell lung cancer. Three hOGG1 haplotype-tagging SNPs (htSNP) were genotyped in PCR-restriction fragment length polymorphism assays, and one htSNP was genotyped in a PCR-single-strand conformation polymorphism assay in case-control studies of 217 NSCLC patients and 226 healthy controls...
December 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/28038351/microrna-29-impairs-the-early-phase-of-reprogramming-process-by-targeting-active-dna-demethylation-enzymes-and-wnt-signaling
#17
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
#18
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...
February 2017: 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
#19
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/28030819/hyperhomocysteinemia-results-from-and-promotes-hepatocellular-carcinoma-via-cyp450-metabolism-by-cyp2j2-dna-methylation
#20
Donghong Zhang, Jinli Lou, Xu Zhang, Lin Zhang, Fei Wang, Danfei Xu, Na Niu, Yidong Wang, Yue Wu, Wei Cui
Hyperhomocysteinemia (HHcy) can result from liver disease or dysfunction and further alters intracellular lipid metabolism. Cytochrome P450 (CYP) arachidonic acid epoxygenases are expressed in human cancers and promote cancer metastasis. This study explored the interaction of Hcy and CYP450 metabolism in hepatocellular carcinoma (HCC). The levels of 4-epoxyeicosatrienoic acid (EET) isomers and their generative enzyme CYP2J2 level as well as intracellular Hcy level were higher in 42 cases of HCC than in paired non-tumor tissue...
December 24, 2016: Oncotarget
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