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https://www.readbyqxmd.com/read/29036642/striking-a-balance-regulation-of-transposable-elements-by-zfp281-and-mll2-in-mouse-embryonic-stem-cells
#1
Qian Dai, Yang Shen, Yan Wang, Xin Wang, Joel Celio Francisco, Zhuojuan Luo, Chengqi Lin
Transposable elements (TEs) compose about 40% of the murine genome. Retrotransposition of active TEs such as LINE-1 (L1) tremendously impacts genetic diversification and genome stability. Therefore, transcription and transposition activities of retrotransposons are tightly controlled. Here, we show that the Krüppel-like zinc finger protein Zfp281 directly binds and suppresses a subset of retrotransposons, including the active young L1 repeat elements, in mouse embryonic stem (ES) cells. In addition, we find that Zfp281-regulated L1s are highly enriched for 5-hydroxymethylcytosine (5hmC) and H3K4me3...
September 25, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29028987/in-silico-structural-modelling-of-multiple-epigenetic-marks-on-dna
#2
Konrad Krawczyk, Samuel Demharter, Bernhard Knapp, Charlotte M Deane, Peter Minary
Summary: There are four known epigenetic cytosine modifications in mammals: 5mC, 5hmC, 5fC and 5caC. The biological effects of 5mC are well understood but the roles of the remaining modifications remain elusive. Experimental and computational studies suggest that a single epigenetic mark has little structural effect but six of them can radically change the structure of DNA to a new form, F-DNA. Investigating the collective effect of multiple epigenetic marks requires the ability to interrogate all possible combinations of epigenetic states (e...
September 25, 2017: Bioinformatics
https://www.readbyqxmd.com/read/29026078/deciphering-tal-effectors-for-5-methylcytosine-and-5-hydroxymethylcytosine-recognition
#3
Yuan Zhang, Lulu Liu, Shengjie Guo, Jinghui Song, Chenxu Zhu, Zongwei Yue, Wensheng Wei, Chengqi Yi
DNA recognition by transcription activator-like effector (TALE) proteins is mediated by tandem repeats that specify nucleotides through repeat-variable diresidues. These repeat-variable diresidues form direct and sequence-specific contacts to DNA bases; hence, TALE-DNA interaction is sensitive to DNA chemical modifications. Here we conduct a thorough investigation, covering all theoretical repeat-variable diresidue combinations, for their recognition capabilities for 5-methylcytosine and 5-hydroxymethylcytosine, two important epigenetic markers in higher eukaryotes...
October 12, 2017: Nature Communications
https://www.readbyqxmd.com/read/29020633/erasure-of-tet-oxidized-5-methylcytosine-by-a-srap-nuclease
#4
Soo-Mi Kweon, Bing Zhu, Yibu Chen, L Aravind, Shuang-Yong Xu, Douglas E Feldman
Enzymatic oxidation of 5-methylcytosine (5mC) in DNA by the Tet dioxygenases reprograms genome function in embryogenesis and postnatal development. Tet-oxidized derivatives of 5mC such as 5-hydroxymethylcytosine (5hmC) act as transient intermediates in DNA demethylation or persist as durable marks, yet how these alternative fates are specified at individual CpGs is not understood. Here, we report that the SOS response-associated peptidase (SRAP) domain protein Srap1, the mammalian ortholog of an ancient protein superfamily associated with DNA damage response operons in bacteria, binds to Tet-oxidized forms of 5mC in DNA and catalyzes turnover of these bases to unmodified cytosine by an autopeptidase-coupled nuclease...
October 10, 2017: Cell Reports
https://www.readbyqxmd.com/read/28993426/effect-of-diabetes-status-and-hyperglycemia-on-global-dna-methylation-and-hydroxymethylation
#5
Jairo Arturo Pinzón-Cortés, Angelina Perna-Chaux, Nicolás Steven Rojas-Villamizar, Angelica Diaz-Basabe, Diana Carolina Polania-Villanueva, María Fernanda Jacome, Carlos Olimpo Mendivil, Helena Groot, Valeriano López-Segura
Type 2 diabetes mellitus (T2DM) is characterized by oxidative stress that could lead to chronic micro- and macro-vascular complications. We hypothesized that some of the target organ damage is mediated by oxidative alterations in epigenetic mechanisms involving DNA methylation (5mC) and DNA hydroxymethylation (5hmC). We analyzed global DNA methylation and hydroxymethylation in peripheral blood cells in well-controlled and poorly controlled patients with type 2 diabetes mellitus and compared them to healthy controls...
October 9, 2017: Endocrine Connections
https://www.readbyqxmd.com/read/28973458/tet2-and-tdg-mediated-changes-are-required-for-the-acquisition-of-distinct-histone-modifications-in-divergent-terminal-differentiation-of-myeloid-cells
#6
Antonio Garcia-Gomez, Tianlu Li, Martin Kerick, Francesc Català-Moll, Natalia R Comet, Javier Rodríguez-Ubreva, Lorenzo de la Rica, Miguel R Branco, Javier Martín, Esteban Ballestar
The plasticity of myeloid cells is illustrated by a diversity of functions including their role as effectors of innate immunity as macrophages (MACs) and bone remodelling as osteoclasts (OCs). TET2, a methylcytosine dioxygenase highly expressed in these cells and frequently mutated in myeloid leukemias, may be a key contributor to this plasticity. Through transcriptomic and epigenomic analyses, we investigated 5-methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC) and gene expression changes in two divergent terminal myeloid differentiation processes, namely MAC and OC differentiation...
September 29, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28969028/cytosine-5-hydroxymethylation-regulates-vhl-gene-expression-in-renal-clear-cell-carcinoma
#7
En-Guang Ma, Yu-Feng Bai, Wei Cao, Yan Cao, Yong-Gang Huang, Huan-Chen Cheng, Rui-Hua An
Cytosine5-hyxymethylation (5hmC)which is a new epigenetic modification form plays important roles in the development and progression of tumors. In the present study, we observed that levels of 5hmC in the promoter region of Von Hippel-Lindau (VHL) were lower in 97 samples of renal clear cell carcinoma tissue than in matched adjacent benign tissues. Moreover, when the cancer tissue samples were divided based on pathological staging, VHL expression and the level of 5hmC in the VHL promoter were both lower in pathological grade III tumors than in grades I or II...
September 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28945496/mouse-olfactory-bulb-methylome-and-hydroxymethylome-maps-reveal-noncanonical-active-turnover-of-dna-methylation
#8
Qin Ma, Huan Lu, Ziying Xu, Yuanyuan Zhou, Weimin Ci
Hydroxylation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) by TET enzymes presents a particular regulatory mechanism in the mammalian brain. However, although methylation and hydroxymethylation of cytosines in non-CpG contexts have been reported, these mechanisms remain poorly understood. Here, we applied TAB-seq and oxBS-seq selectively to detect 5hmC and 5mC at base resolution in olfactory bulb derived from female mice. We found that active turnover of 5mC to 5hmC occurred in both CpG and non-CpG contexts...
September 25, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28940661/dna-methylation-in-embryo-development-epigenetic-impact-of-art-assisted-reproductive-technologies
#9
REVIEW
Sebastian Canovas, Pablo J Ross, Gavin Kelsey, Pilar Coy
DNA methylation can be considered a component of epigenetic memory with a critical role during embryo development, and which undergoes dramatic reprogramming after fertilization. Though it has been a focus of research for many years, the reprogramming mechanism is still not fully understood. Recent results suggest that absence of maintenance at DNA replication is a major factor, and that there is an unexpected role for TET3-mediated oxidation of 5mC to 5hmC in guarding against de novo methylation. Base-resolution and genome-wide profiling methods are enabling more comprehensive assessments of the extent to which ART might impair DNA methylation reprogramming, and which sequence elements are most vulnerable...
September 21, 2017: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/28934725/prenatal-exposure-to-mercury-associations-with-global-dna-methylation-and-hydroxymethylation-in-cord-blood-and-in-childhood
#10
Andres Cardenas, Sheryl L Rifas-Shiman, Lode Godderis, Radu-Corneliu Duca, Ana Navas-Acien, Augusto A Litonjua, Dawn L DeMeo, Kasey J Brennan, Chitra J Amarasiriwardena, Marie-France Hivert, Matthew W Gillman, Emily Oken, Andrea A Baccarelli
BACKGROUND: Mercury is a global pollutant, and prenatal exposure is associated with adverse health effects. To date, no studies have evaluated the association between prenatal mercury exposure and DNA hydroxymethylation, an epigenetic modification important for tissue differentiation and embryonic development. OBJECTIVES: We sought to evaluate the association between prenatal mercury exposure and offspring global DNA methylation and hydroxymethylation at birth and test for persistence of the association in childhood...
August 29, 2017: Environmental Health Perspectives
https://www.readbyqxmd.com/read/28930980/immunostaining-for-dna-modifications-computational-analysis-of-confocal-images
#11
Ashley H Ramsawhook, Lara C Lewis, Maria Eleftheriou, Abdulkadir Abakir, Paulina Durczak, Robert Markus, Seema Rajani, Nicholas R F Hannan, Beth Coyle, Alexey Ruzov
For several decades, 5-methylcytosine (5mC) has been thought to be the only DNA modification with a functional significance in metazoans. The discovery of enzymatic oxidation of 5mC to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) as well as detection of N6-methyladenine (6mA) in the DNA of multicellular organisms provided additional degrees of complexity to the epigenetic research. According to a growing body of experimental evidence, these novel DNA modifications may play specific roles in different cellular and developmental processes...
September 7, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28930672/histone-h3-methylated-at-arginine-17-is-essential-for-reprogramming-the-paternal-genome-in-zygotes
#12
Yuki Hatanaka, Takeshi Tsusaka, Natsumi Shimizu, Kohtaro Morita, Takehiro Suzuki, Shinichi Machida, Manabu Satoh, Arata Honda, Michiko Hirose, Satoshi Kamimura, Narumi Ogonuki, Toshinobu Nakamura, Kimiko Inoue, Yoshihiko Hosoi, Naoshi Dohmae, Toru Nakano, Hitoshi Kurumizaka, Kazuya Matsumoto, Yoichi Shinkai, Atsuo Ogura
At fertilization, the paternal genome undergoes extensive reprogramming through protamine-histone exchange and active DNA demethylation, but only a few maternal factors have been defined in these processes. We identified maternal Mettl23 as a protein arginine methyltransferase (PRMT), which most likely catalyzes the asymmetric dimethylation of histone H3R17 (H3R17me2a), as indicated by in vitro assays and treatment with TBBD, an H3R17 PRMT inhibitor. Maternal histone H3.3, which is essential for paternal nucleosomal assembly, is unable to be incorporated into the male pronucleus when it lacks R17me2a...
September 19, 2017: Cell Reports
https://www.readbyqxmd.com/read/28926578/tet-mediated-dna-hydroxymethylation-regulates-retinal-neurogenesis-by-modulating-cell-extrinsic-signaling-pathways
#13
Pawat Seritrakul, Jeffrey M Gross
DNA hydroxymethylation has recently been shown to play critical roles in regulating gene expression and terminal differentiation events in a variety of developmental contexts. However, little is known about its function during eye development. Methylcytosine dioxygenases of the Tet family convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), an epigenetic mark thought to serve as a precursor for DNA demethylation and as a stable mark in neurons. Here, we report a requirement for Tet activity during zebrafish retinal neurogenesis...
September 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28925386/5-hydroxymethylcytosine-signatures-in-circulating-cell-free-dna-as-diagnostic-biomarkers-for-human-cancers
#14
Wenshuai Li, Xu Zhang, Xingyu Lu, Lei You, Yanqun Song, Zhongguang Luo, Jun Zhang, Ji Nie, Wanwei Zheng, Diannan Xu, Yaping Wang, Yuanqiang Dong, Shulin Yu, Jun Hong, Jianping Shi, Hankun Hao, Fen Luo, Luchun Hua, Peng Wang, Xiaoping Qian, Fang Yuan, Lianhuan Wei, Ming Cui, Taiping Zhang, Quan Liao, Menghua Dai, Ziwen Liu, Ge Chen, Katherine Meckel, Sarbani Adhikari, Guifang Jia, Marc B Bissonnette, Xinxiang Zhang, Yupei Zhao, Wei Zhang, Chuan He, Jie Liu
DNA modifications such as 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) are epigenetic marks known to affect global gene expression in mammals. Given their prevalence in the human genome, close correlation with gene expression and high chemical stability, these DNA epigenetic marks could serve as ideal biomarkers for cancer diagnosis. Taking advantage of a highly sensitive and selective chemical labeling technology, we report here the genome-wide profiling of 5hmC in circulating cell-free DNA (cfDNA) and in genomic DNA (gDNA) of paired tumor and adjacent tissues collected from a cohort of 260 patients recently diagnosed with colorectal, gastric, pancreatic, liver or thyroid cancer and normal tissues from 90 healthy individuals...
October 2017: Cell Research
https://www.readbyqxmd.com/read/28923016/5-hydroxymethylcytosine-is-highly-dynamic-across-human-fetal-brain-development
#15
Helen Spiers, Eilis Hannon, Leonard C Schalkwyk, Nicholas J Bray, Jonathan Mill
BACKGROUND: Epigenetic processes play a key role in orchestrating transcriptional regulation during the development of the human central nervous system. We previously described dynamic changes in DNA methylation (5mC) occurring during human fetal brain development, but other epigenetic processes operating during this period have not been extensively explored. Of particular interest is DNA hydroxymethylation (5hmC), a modification that is enriched in the human brain and hypothesized to play an important role in neuronal function, learning and memory...
September 18, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28870782/the-role-of-tet-mediated-dna-hydroxymethylation-in-prostate-cancer
#16
E Smeets, A G Lynch, S Prekovic, T Van den Broeck, L Moris, C Helsen, S Joniau, F Claessens, C E Massie
Ten-eleven translocation (TET) proteins are recently characterized dioxygenases that regulate demethylation by oxidizing 5-methylcytosine to 5-hydroxymethylcytosine and further derivatives. The recent finding that 5hmC is also a stable and independent epigenetic modification indicates that these proteins play an important role in diverse physiological and pathological processes such as neural and tumor development. Both the genomic distribution of (hydroxy)methylation and the expression and activity of TET proteins are dysregulated in a wide range of cancers including prostate cancer...
September 1, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28870206/3-6-dihydroxyflavone-regulates-microrna-34a-through-dna-methylation
#17
Xiaoli Peng, Hui Chang, Junli Chen, Qianyong Zhang, Xiaoping Yu, Mantian Mi
BACKGROUND: Breast cancer is the common cancer in China. In previous study, we determined that 3,6-dihydroxyflavone (3,6-DHF) increases miR-34a significantly in breast carcinogenesis, but the mechanism remains unclear. METHODS: We used qRT-PCR to analyze miR-34a and ten-eleven translocation (TET)1, TET2, TET3 levels in breast cancer cells. With a cellular breast carcinogenesis model and an experimental model of carcinogenesis in rats, TET1 levels were evaluated by western blot analysis and immunofluorescence...
September 5, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28860502/bi-directional-and-shared-epigenomic-signatures-following-proton-and-56-fe-irradiation
#18
Soren Impey, Timothy Jopson, Carl Pelz, Amanuel Tafessu, Fatema Fareh, Damian Zuloaga, Tessa Marzulla, Lara-Kirstie Riparip, Blair Stewart, Susanna Rosi, Mitchell S Turker, Jacob Raber
The brain's response to radiation exposure is an important concern for patients undergoing cancer therapy and astronauts on long missions in deep space. We assessed whether this response is specific and prolonged and is linked to epigenetic mechanisms. We focused on the response of the hippocampus at early (2-weeks) and late (20-week) time points following whole body proton irradiation. We examined two forms of DNA methylation, cytosine methylation (5mC) and hydroxymethylation (5hmC). Impairments in object recognition, spatial memory retention, and network stability following proton irradiation were observed at the two-week time point and correlated with altered gene expression and 5hmC profiles that mapped to specific gene ontology pathways...
August 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28858762/ultrasensitive-electrochemiluminescence-immunosensor-for-5-hydroxymethylcytosine-detection-based-on-fe3o4-sio2-nanoparticles-and-pamam-dendrimers
#19
Wenjing Jiang, Linni Wu, Junling Duan, Huanshun Yin, Shiyun Ai
An ultrasensitive sandwiched electrochemiluminescence (ECL) immunosensor was developed for 5-hydroxymethylcytosine (5hmC) detection in genomic DNA by using Fe3O4@SiO2 core-shell magnetic nanomaterial as a immobilization matrix for anti-5hmC antibody, PAMAM conjugated avidin and Ru(bpy)2(phen-5-NH2)(PF6)2 as signal amplification unit. Importantly, Fe3O4@SiO2 nanoparticles were verified to not only possess enormous surface for loading antibody by amido link, but also exhibit excellent bioactivity. With the dual signal amplification strategy, the ECL immunosensor showed wide detection range from 0...
August 12, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/28855337/an-epigenetic-switch-repressing-tet1-in-gonadotropes-activates-the-reproductive-axis
#20
Yahav Yosefzon, Cfir David, Anna Tsukerman, Lilach Pnueli, Sen Qiao, Ulrich Boehm, Philippa Melamed
The TET enzymes catalyze conversion of 5-methyl cytosine (5mC) to 5-hydroxymethyl cytosine (5hmC) and play important roles during development. TET1 has been particularly well-studied in pluripotent stem cells, but Tet1-KO mice are viable, and the most marked defect is abnormal ovarian follicle development, resulting in impaired fertility. We hypothesized that TET1 might play a role in the central control of reproduction by regulating expression of the gonadotropin hormones, which are responsible for follicle development and maturation and ovarian function...
September 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
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